rs6647
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000295.5(SERPINA1):āc.710T>Cā(p.Val237Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,609,248 control chromosomes in the GnomAD database, including 47,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. V237V) has been classified as Likely benign.
Frequency
Consequence
NM_000295.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINA1 | NM_000295.5 | c.710T>C | p.Val237Ala | missense_variant | 3/5 | ENST00000393087.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINA1 | ENST00000393087.9 | c.710T>C | p.Val237Ala | missense_variant | 3/5 | 1 | NM_000295.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.298 AC: 45061AN: 151122Hom.: 8912 Cov.: 30
GnomAD3 exomes AF: 0.210 AC: 52480AN: 250450Hom.: 7248 AF XY: 0.205 AC XY: 27722AN XY: 135346
GnomAD4 exome AF: 0.216 AC: 315025AN: 1458008Hom.: 38288 Cov.: 33 AF XY: 0.213 AC XY: 154538AN XY: 725512
GnomAD4 genome ? AF: 0.298 AC: 45104AN: 151240Hom.: 8923 Cov.: 30 AF XY: 0.295 AC XY: 21772AN XY: 73860
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 09, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 13, 2013 | Benign based on MAF. See note for OMIM entry (which is responsible for the "wit h pathogenic allele" association in dbSNP) - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 03, 2023 | - - |
Alpha-1-antitrypsin deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | curation | Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital | Dec 08, 2014 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
PI, M1A Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 15, 2016 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
PI M1-ALA213 Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 15, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at