15-39588617-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003246.4(THBS1):c.1563C>T(p.Asn521Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,476 control chromosomes in the GnomAD database, including 790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 68 hom., cov: 32)

Exomes 𝑓: 0.030 ( 722 hom. )

Consequence

THBS1
NM_003246.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.21

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-AS1 (HGNC:55224): (THBS1 antisense RNA 1)

THBS1-AS1 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 15-39588617-C-T is Benign according to our data. Variant chr15-39588617-C-T is described in ClinVar as [Benign]. Clinvar id is 403536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3369/152276) while in subpopulation NFE AF= 0.0338 (2297/68002). AF 95% confidence interval is 0.0326. There are 68 homozygotes in gnomad4. There are 1531 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3369 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4 link	c.1563C>T	p.Asn521Asn	synonymous_variant	Exon 10 of 22	ENST00000260356.6	NP_003237.2	P07996-1
THBS1	XM_047432980.1 link	c.1563C>T	p.Asn521Asn	synonymous_variant	Exon 10 of 22		XP_047288936.1
THBS1	XM_011521971.3 link	c.1472-342C>T		intron_variant	Intron 9 of 20		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
THBS1	ENST00000260356.6 link	c.1563C>T	p.Asn521Asn	synonymous_variant	Exon 10 of 22	1	NM_003246.4	ENSP00000260356.5	P07996-1
THBS1	ENST00000497720.1 link	n.359C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
THBS1-AS1	ENST00000616754.1 link	n.266G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
FSIP1	ENST00000642527.1 link	n.*215-43G>A		intron_variant	Intron 3 of 3			ENSP00000496642.1	A0A2R8YHB5

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3368

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0338

Gnomad OTH

AF:

0.0267

GnomAD3 exomes

AF:

0.0238

AC:

5918

AN:

248838

Hom.:

AF XY:

0.0245

AC XY:

3295

AN XY:

134470

show subpopulations

Gnomad AFR exome

AF:

0.00599

Gnomad AMR exome

AF:

0.0276

Gnomad ASJ exome

AF:

0.0379

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00858

Gnomad NFE exome

AF:

0.0323

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0301

AC:

43886

AN:

1459200

Hom.:

722

Cov.:

AF XY:

0.0300

AC XY:

21764

AN XY:

725820

show subpopulations

Gnomad4 AFR exome

AF:

0.00544

Gnomad4 AMR exome

AF:

0.0280

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.00978

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0289

GnomAD4 genome

AF:

0.0221

AC:

3369

AN:

152276

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1531

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.0433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.00772

Gnomad4 NFE

AF:

0.0338

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0276

Hom.:

Bravo

AF:

0.0230

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0369

EpiControl

AF:

0.0397

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: Silent, not in splice consensus -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

THBS1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.46

CADD

Benign

DANN

Benign

0.81

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