rs2228263

Positions:

chr15-39593100-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003246.4(THBS1):c.2868T>C(p.Asp956Asp) 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 (★★).

Frequency

Genomes: 𝑓 0.16 ( 2143 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18664 hom. )

Consequence

THBS1
NM_003246.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.18

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:

THBS1 (HGNC:):

THBS1 links:

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

FSIP1 links:

Genome browser will be placed here

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	Protein	UniProt
THBS1	NM_003246.4 linkuse as main transcript	c.2868T>C	p.Asp956Asp	synonymous_variant	18/22	ENST00000260356.6	NP_003237.2	P07996-1
THBS1	XM_047432980.1 linkuse as main transcript	c.2868T>C	p.Asp956Asp	synonymous_variant	18/22		XP_047288936.1
THBS1	XM_011521971.3 linkuse as main transcript	c.2694T>C	p.Asp898Asp	synonymous_variant	17/21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THBS1	ENST00000260356.6 linkuse as main transcript	c.2868T>C	p.Asp956Asp	synonymous_variant	18/22	1	NM_003246.4	ENSP00000260356.5	P07996-1
THBS1	ENST00000484734.1 linkuse as main transcript	n.56T>C		non_coding_transcript_exon_variant	1/4	5
FSIP1	ENST00000642527.1 linkuse as main transcript	n.*214+955A>G		intron_variant				ENSP00000496642.1	A0A2R8YHB5

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24128

AN:

151916

Hom.:

2136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0674

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.127

AC:

29838

AN:

234862

Hom.:

2336

AF XY:

0.127

AC XY:

16024

AN XY:

126252

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0842

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.000551

Gnomad SAS exome

AF:

0.0678

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.155

AC:

224194

AN:

1444940

Hom.:

18664

Cov.:

AF XY:

0.153

AC XY:

109671

AN XY:

717568

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.0889

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0721

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.159

AC:

24165

AN:

152034

Hom.:

2143

Cov.:

AF XY:

0.153

AC XY:

11366

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0673

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.164

Hom.:

2504

Bravo

AF:

0.159

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

THBS1-related disorder

Benign:1

Benign, no assertion criteria provided

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.8

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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