dbSNP rs9283850: THBS2:c.1301-15C>T (chr6-169237361-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003247.5(THBS2):c.1301-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,611,876 control chromosomes in the GnomAD database, including 234,862 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 28058 hom., cov: 35)

Exomes 𝑓: 0.53 ( 206804 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

14 publications found

Variant links:

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2 links:

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

THBS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.1301-15C>T		intron_variant	Intron 8 of 21	ENST00000617924.6	NP_003238.2	P35442

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6 link	c.1301-15C>T		intron_variant	Intron 8 of 21	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90455

AN:

152070

Hom.:

28017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.611

GnomAD2 exomes

AF:

0.572

AC:

142018

AN:

248138

AF XY:

0.558

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.901

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.501

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.526

AC:

767096

AN:

1459688

Hom.:

206804

Cov.:

AF XY:

0.523

AC XY:

379971

AN XY:

726120

show subpopulations

African (AFR)

AF:

0.729

AC:

24416

AN:

33472

American (AMR)

AF:

0.687

AC:

30710

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12968

AN:

26124

East Asian (EAS)

AF:

0.891

AC:

35349

AN:

39692

South Asian (SAS)

AF:

0.499

AC:

42995

AN:

86228

European-Finnish (FIN)

AF:

0.481

AC:

25023

AN:

52002

Middle Eastern (MID)

AF:

0.505

AC:

2911

AN:

5768

European-Non Finnish (NFE)

AF:

0.503

AC:

559551

AN:

1111356

Other (OTH)

AF:

0.550

AC:

33173

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

18194

36388

54581

72775

90969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16412

32824

49236

65648

82060

<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:

0.595

AC:

90552

AN:

152188

Hom.:

28058

Cov.:

AF XY:

0.593

AC XY:

44093

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.726

AC:

30178

AN:

41550

American (AMR)

AF:

0.633

AC:

9672

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1803

AN:

3470

East Asian (EAS)

AF:

0.898

AC:

4639

AN:

5166

South Asian (SAS)

AF:

0.516

AC:

2489

AN:

4828

European-Finnish (FIN)

AF:

0.479

AC:

5072

AN:

10592

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.510

AC:

34682

AN:

67978

Other (OTH)

AF:

0.612

AC:

1294

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1905

3810

5716

7621

9526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.543

Hom.:

69994

Bravo

AF:

0.617

Asia WGS

AF:

0.711

AC:

2471

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.57

PhyloP100

1.2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over