Variant rs2229364 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003246.4(THBS1):c.1290G>A(p.Lys430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,610,996 control chromosomes in the GnomAD database, including 15,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1280 hom., cov: 33)

Exomes 𝑓: 0.13 ( 14082 hom. )

Consequence

THBS1
NM_003246.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.47

Variant links:

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]

THBS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-39587516-G-A is Benign according to our data. Variant chr15-39587516-G-A is described in ClinVar as [Benign]. Clinvar id is 403534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
THBS1	NM_003246.4 linkuse as main transcript	c.1290G>A	p.Lys430=	synonymous_variant	8/22	ENST00000260356.6
THBS1	XM_047432980.1 linkuse as main transcript	c.1290G>A	p.Lys430=	synonymous_variant	8/22
THBS1	XM_011521971.3 linkuse as main transcript	c.1290G>A	p.Lys430=	synonymous_variant	8/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS1	ENST00000260356.6 linkuse as main transcript	c.1290G>A	p.Lys430=	synonymous_variant	8/22	1	NM_003246.4	P1	P07996-1
THBS1	ENST00000466755.1 linkuse as main transcript	n.65G>A		non_coding_transcript_exon_variant	1/2	2
THBS1	ENST00000497720.1 linkuse as main transcript	n.86G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18276

AN:

152168

Hom.:

1284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.134

AC:

33218

AN:

247448

Hom.:

2761

AF XY:

0.139

AC XY:

18581

AN XY:

133574

show subpopulations

Gnomad AFR exome

AF:

0.0787

Gnomad AMR exome

AF:

0.0898

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.131

AC:

190797

AN:

1458710

Hom.:

14082

Cov.:

AF XY:

0.133

AC XY:

96335

AN XY:

725150

show subpopulations

Gnomad4 AFR exome

AF:

0.0880

Gnomad4 AMR exome

AF:

0.0929

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.120

AC:

18266

AN:

152286

Hom.:

1280

Cov.:

AF XY:

0.122

AC XY:

9120

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0819

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.115

Hom.:

743

Bravo

AF:

0.122

Asia WGS

AF:

0.247

AC:

863

AN:

3478

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 21, 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over