ClinVar Miner

Submissions for variant NM_000295.5(SERPINA1):c.-5+1G>A

dbSNP: rs775786225
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003064236 SCV003442799 pathogenic Alpha-1-antitrypsin deficiency 2023-05-02 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant does not significantly alter or has an unclear effect on SERPINA1 gene expression (PMID: 12220457). ClinVar contains an entry for this variant (Variation ID: 2137619). This variant has been observed in individual(s) with clinical features consistent with SERPINA1 related conditions (PMID: 12220457; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the SERPINA1 gene. It does not change the encoded amino acid sequence of the SERPINA1 protein. It affects a nucleotide within the consensus splice site.
Baylor Genetics RCV003064236 SCV004203119 pathogenic Alpha-1-antitrypsin deficiency 2024-03-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV003064236 SCV004847941 likely pathogenic Alpha-1-antitrypsin deficiency 2015-04-03 criteria provided, single submitter clinical testing The c.-5+1G>A variant in SERPINA1 has been previously reported in 1 compound heterozygous individual with emphysema and in 1 compound heterozygous individual with chronic obstructive pulmonary disease (COPD), and segregated with disease in 1 compound heterozygous individual with COPD (Seixas 2002, Lara 2014). Data from large population studies is insufficient to assess the frequency of this variant. This variant occurs in the invariant region (+/- 1, 2) of the splice consensus sequence of a non-coding exon and functional studies indicate this variant leads to altered splicing which is predicted to lead to an abnormal or absent protein (Lara 2014). In summary, although additional studies are required to fully establish its clinical significance, the c.-5+1G>A variant is likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.