rs28929474
| Pi-Z allele |
| Orientation | minus |
| Stabilized | minus |
| Geno | Mag | Summary |
|---|---|---|
| (A;A) | 5.5 | Alpha-1 Antitrypsin Deficiency |
| (A;G) | 3 | Carrier for Alpha-1 Antitrypsin Deficiency |
| (G;G) | 0 | common in complete genomics |
| Reference | GRCh38 38.1/141 |
| Chromosome | 14 |
| Position | 94378610 |
| Gene | SERPINA1 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs28929474 |
| dbSNP (classic) | rs28929474 |
| ClinGen | rs28929474 |
| ebi | rs28929474 |
| HLI | rs28929474 |
| Exac | rs28929474 |
| Gnomad | rs28929474 |
| Varsome | rs28929474 |
| LitVar | rs28929474 |
| Map | rs28929474 |
| PheGenI | rs28929474 |
| Biobank | rs28929474 |
| 1000 genomes | rs28929474 |
| hgdp | rs28929474 |
| ensembl | rs28929474 |
| geneview | rs28929474 |
| scholar | rs28929474 |
| rs28929474 | |
| pharmgkb | rs28929474 |
| gwascentral | rs28929474 |
| openSNP | rs28929474 |
| 23andMe | rs28929474 |
| SNPshot | rs28929474 |
| SNPdbe | rs28929474 |
| MSV3d | rs28929474 |
| GWAS Ctlg | rs28929474 |
| GMAF | 0.007346 |
| Max Magnitude | 5.5 |
rs28929474, also known as Glu342Lys as well as E366K (and Glu366Lys), is a SNP in the serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 SERPINA1 gene.
This SNP is the one most frequently leading, when homozygous, to the complications of alpha-1 antitrypsin deficiency and the associated high risk of emphysema and liver disease. Between 1 - 2% of US Caucasians are thought to be (heterozygous) carriers for this SNP, leading some associations, like the Alpha-1 Foundation, to call for mass carrier screening.
Carriers of Alpha-1-antitrypsin have also been shown to be at risk for Granulomatosis with Polyangiitis GPA [PMID 11161981]
- 23andMe blog rs28929474(T) increases odds of liver disease in cystic fibrosis patients by 4.17 times. (T;T) at both copies of this SNP causes alpha-1 antitrypsin deficiency; note use of opposite strand nomenclature by this company.
[PMID 21138453] Heterozygosity for the alpha1-antitrypsin Z allele may confer genetic risk of cholangiocarcinoma
| ClinVar | |
|---|---|
| Risk | Rs28929474(A;A) |
| Alt | Rs28929474(A;A) |
| Reference | Rs28929474(G;G) |
| Significance | Other |
| Disease | PI Z PI Z(AUGSBURG) PI Z(TUN) Alpha-1-antitrypsin deficiency FRAXE not provided |
| Variation | info |
| Gene | SERPINA1 |
| CLNDBN | PI Z PI Z(AUGSBURG) PI Z(TUN) Alpha-1-antitrypsin deficiency FRAXE not provided |
| Reversed | 1 |
| HGVS | NC_000014.8:g.94844947C>T |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000019567.3, RCV000019594.2, RCV000019595.2, RCV000148877.8, RCV000194811.1, RCV000255454.2, |
[PMID 28146470
] Rare and low-frequency coding variants alter human adult height.
[PMID 22426792] Serum levels and genotype distribution of alpha1-antitrypsin in the general population.
[PMID 20170533] Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study.
[PMID 3264419] Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model.
[PMID 3259592] Alpha 1-antitrypsin deficiency associated with panniculitis
[PMID 2904702] Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation.
[PMID 16608528] Genetic polymorphisms and susceptibility to lung disease.
[PMID 25454901] Prevalence of alpha-1 antitrypsin high-risk variants in Mexican mestizo population and their association with lung function values
[PMID 26831755] A study of common Mendelian disease carriers across ageing British cohorts: meta-analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height.
[PMID 31298815] SERPINA1 gene polymorphisms in a population-based ALSPAC cohort.
[PMID 31517326] SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis.
