chr15-39593085-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003246.4(THBS1):c.2853C>T(p.Asp951=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,600,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
THBS1
NM_003246.4 synonymous
NM_003246.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.801
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 15-39593085-C-T is Benign according to our data. Variant chr15-39593085-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048631.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.801 with no splicing effect.
BS2
High AC in GnomAd4 at 161 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.2853C>T | p.Asp951= | synonymous_variant | 18/22 | ENST00000260356.6 | |
THBS1 | XM_047432980.1 | c.2853C>T | p.Asp951= | synonymous_variant | 18/22 | ||
THBS1 | XM_011521971.3 | c.2679C>T | p.Asp893= | synonymous_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.2853C>T | p.Asp951= | synonymous_variant | 18/22 | 1 | NM_003246.4 | P1 | |
THBS1 | ENST00000484734.1 | n.41C>T | non_coding_transcript_exon_variant | 1/4 | 5 | ||||
FSIP1 | ENST00000642527.1 | c.*214+970G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 161AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000245 AC: 58AN: 236862Hom.: 0 AF XY: 0.000204 AC XY: 26AN XY: 127426
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GnomAD4 exome AF: 0.000110 AC: 159AN: 1448232Hom.: 0 Cov.: 32 AF XY: 0.000101 AC XY: 73AN XY: 719546
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GnomAD4 genome AF: 0.00106 AC: 161AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00107 AC XY: 80AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
THBS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 25, 2019 | This variant is classified as likely 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
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at