rs5918
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BS3BP2BP4BA1
This summary comes from the ClinGen Evidence Repository: The ITGB3 c.176T>C (p.Leu59Pro) missense variant has been reported many times in the literature as an alloantigenic site. This variant has been observed in cis with several other Glanzmann thrombasthenia variants, including the pathogenic c.224del frameshift variant (PMID:25728920). It is present in gnomAD at an overall allele frequency of 0.1223 (and 0.1550 in the non-Finnish European population). Computational evidence suggest no impact on the gene/gene product, with a REVEL score of 0.217. Functional studies in CHO cells have shown no deleterious effect on surface expression or fibrinogen binding (PMID:10727448). In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BS3, BP2, BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA123235/MONDO:0010119/011
Frequency
Consequence
NM_000212.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITGB3 | NM_000212.3 | c.176T>C | p.Leu59Pro | missense_variant | 3/15 | ENST00000559488.7 | NP_000203.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGB3 | ENST00000559488.7 | c.176T>C | p.Leu59Pro | missense_variant | 3/15 | 1 | NM_000212.3 | ENSP00000452786 | P1 | |
ITGB3 | ENST00000571680.1 | c.176T>C | p.Leu59Pro | missense_variant | 3/9 | 1 | ENSP00000461626 | |||
ITGB3 | ENST00000696963.1 | c.176T>C | p.Leu59Pro | missense_variant | 3/14 | ENSP00000513002 |
Frequencies
GnomAD3 genomes AF: 0.128 AC: 19456AN: 152154Hom.: 1387 Cov.: 32
GnomAD3 exomes AF: 0.121 AC: 30400AN: 251122Hom.: 2106 AF XY: 0.123 AC XY: 16665AN XY: 135738
GnomAD4 exome AF: 0.141 AC: 206046AN: 1461664Hom.: 15584 Cov.: 34 AF XY: 0.140 AC XY: 101833AN XY: 727142
GnomAD4 genome AF: 0.128 AC: 19457AN: 152272Hom.: 1387 Cov.: 32 AF XY: 0.125 AC XY: 9315AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2021 | This variant is associated with the following publications: (PMID: 29462793, 29965811, 29038237, 29117201, 11723016, 2565345, 18657307, 22133274, 23155369, 20472470, 10727448, 15826939, 11028489, 24720773, 21919778, 21109038, 21813062, 19245802, 19388931, 18214290, 15609125, 19530321, 10195947, 21353223, 18836720, 21241403) - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Glanzmann thrombasthenia Benign:2
Benign, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Jun 18, 2020 | The ITGB3 c.176T>C (p.Leu59Pro) missense variant has been reported many times in the literature as an alloantigenic site. This variant has been observed in cis with several other Glanzmann thrombasthenia variants, including the pathogenic c.224del frameshift variant (PMID: 25728920). It is present in gnomAD at an overall allele frequency of 0.1223 (and 0.1550 in the non-Finnish European population). Computational evidence suggest no impact on the gene/gene product, with a REVEL score of 0.217. Functional studies in CHO cells have shown no deleterious effect on surface expression or fibrinogen binding (PMID: 10727448). In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BS3, BP2, BP4. - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | May 31, 2017 | BA1, BP4, BP6; This alteration has an allele frequency that is greater than 5% healthy populations (ExAC/gnomAD), is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
PL(A1)/(A2) ALLOANTIGEN POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jan 01, 2007 | - - |
Myocardial infarction, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jan 01, 2007 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at