rs2228263
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003246.4(THBS1):āc.2868T>Cā(p.Asp956=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,596,974 control chromosomes in the GnomAD database, including 20,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.16 ( 2143 hom., cov: 32)
Exomes š: 0.16 ( 18664 hom. )
Consequence
THBS1
NM_003246.4 synonymous
NM_003246.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.18
Genes affected
THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 15-39593100-T-C is Benign according to our data. Variant chr15-39593100-T-C is described in ClinVar as [Benign]. Clinvar id is 403538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.18 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.2868T>C | p.Asp956= | synonymous_variant | 18/22 | ENST00000260356.6 | |
THBS1 | XM_047432980.1 | c.2868T>C | p.Asp956= | synonymous_variant | 18/22 | ||
THBS1 | XM_011521971.3 | c.2694T>C | p.Asp898= | synonymous_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.2868T>C | p.Asp956= | synonymous_variant | 18/22 | 1 | NM_003246.4 | P1 | |
THBS1 | ENST00000484734.1 | n.56T>C | non_coding_transcript_exon_variant | 1/4 | 5 | ||||
FSIP1 | ENST00000642527.1 | c.*214+955A>G | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.159 AC: 24128AN: 151916Hom.: 2136 Cov.: 32
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GnomAD3 exomes AF: 0.127 AC: 29838AN: 234862Hom.: 2336 AF XY: 0.127 AC XY: 16024AN XY: 126252
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GnomAD4 exome AF: 0.155 AC: 224194AN: 1444940Hom.: 18664 Cov.: 33 AF XY: 0.153 AC XY: 109671AN XY: 717568
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GnomAD4 genome ? AF: 0.159 AC: 24165AN: 152034Hom.: 2143 Cov.: 32 AF XY: 0.153 AC XY: 11366AN XY: 74340
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
THBS1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at