chr15-39588157-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003246.4(THBS1):c.1410C>T(p.Asn470Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,928 control chromosomes in the GnomAD database, including 21,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4637 hom., cov: 33)

Exomes 𝑓: 0.14 ( 17332 hom. )

Consequence

THBS1
NM_003246.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.07

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 15-39588157-C-T is Benign according to our data. Variant chr15-39588157-C-T is described in ClinVar as Benign. ClinVar VariationId is 403535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	NM_003246.4	MANE Select	c.1410C>T	p.Asn470Asn	synonymous	Exon 9 of 22	NP_003237.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
THBS1	ENST00000260356.6	TSL:1 MANE Select	c.1410C>T	p.Asn470Asn	synonymous	Exon 9 of 22	ENSP00000260356.5
THBS1	ENST00000466755.1	TSL:2	n.185C>T		non_coding_transcript_exon	Exon 2 of 2
THBS1	ENST00000497720.1	TSL:2	n.206C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32111

AN:

151988

Hom.:

4634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.159

AC:

39915

AN:

251390

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.140

AC:

204855

AN:

1461820

Hom.:

17332

Cov.:

AF XY:

0.141

AC XY:

102523

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.414

AC:

13874

AN:

33478

American (AMR)

AF:

0.108

AC:

4830

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3514

AN:

26134

East Asian (EAS)

AF:

0.330

AC:

13109

AN:

39698

South Asian (SAS)

AF:

0.196

AC:

16906

AN:

86244

European-Finnish (FIN)

AF:

0.104

AC:

5535

AN:

53402

Middle Eastern (MID)

AF:

0.203

AC:

1172

AN:

5766

European-Non Finnish (NFE)

AF:

0.122

AC:

136065

AN:

1111984

Other (OTH)

AF:

0.163

AC:

9850

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

9664

19327

28991

38654

48318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5254

10508

15762

21016

26270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.211

AC:

32134

AN:

152108

Hom.:

4637

Cov.:

AF XY:

0.209

AC XY:

15521

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.401

AC:

16625

AN:

41436

American (AMR)

AF:

0.164

AC:

2502

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

463

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1601

AN:

5162

South Asian (SAS)

AF:

0.205

AC:

989

AN:

4818

European-Finnish (FIN)

AF:

0.105

AC:

1113

AN:

10602

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8193

AN:

68002

Other (OTH)

AF:

0.206

AC:

436

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1187

2374

3561

4748

5935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

1459

Bravo

AF:

0.225

Asia WGS

AF:

0.264

AC:

924

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.131

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: Frequency

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.38

(source)

DANN

Benign

0.86

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over