chr17-47287174-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BP4BA1
This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623073/MONDO:0100326/011
Frequency
Consequence
NM_000212.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITGB3 | NM_000212.3 | c.882T>C | p.Pro294= | synonymous_variant | 6/15 | ENST00000559488.7 | NP_000203.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGB3 | ENST00000559488.7 | c.882T>C | p.Pro294= | synonymous_variant | 6/15 | 1 | NM_000212.3 | ENSP00000452786 | P1 | |
ITGB3 | ENST00000571680.1 | c.882T>C | p.Pro294= | synonymous_variant | 6/9 | 1 | ENSP00000461626 | |||
ITGB3 | ENST00000696963.1 | c.882T>C | p.Pro294= | synonymous_variant | 6/14 | ENSP00000513002 |
Frequencies
GnomAD3 genomes AF: 0.105 AC: 15995AN: 152084Hom.: 1009 Cov.: 32
GnomAD3 exomes AF: 0.100 AC: 25242AN: 251236Hom.: 1723 AF XY: 0.103 AC XY: 13938AN XY: 135784
GnomAD4 exome AF: 0.0802 AC: 117232AN: 1461626Hom.: 6043 Cov.: 33 AF XY: 0.0827 AC XY: 60153AN XY: 727118
GnomAD4 genome AF: 0.105 AC: 16029AN: 152202Hom.: 1018 Cov.: 32 AF XY: 0.105 AC XY: 7815AN XY: 74414
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Glanzmann thrombasthenia Benign:2
Benign, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Dec 01, 2022 | After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at