dbSNP rs1478604: THBS1:c.-138T>C (chr15-39581120-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003246.4(THBS1):c.-138T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,698 control chromosomes in the GnomAD database, including 14,649 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 0.40 ( 14620 hom., cov: 33)

Exomes 𝑓: 0.28 ( 29 hom. )

Consequence

THBS1
NM_003246.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.239

Publications

38 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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

THBS1 links:

LOC124903470 (HGNC:):

LOC124903470 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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4 link	c.-138T>C	5_prime_UTR_variant	Exon 1 of 22	ENST00000260356.6	NP_003237.2	P07996-1
THBS1	XM_047432980.1 link	c.-259T>C	5_prime_UTR_variant	Exon 1 of 22		XP_047288936.1
THBS1	XM_011521971.3 link	c.-138T>C	5_prime_UTR_variant	Exon 1 of 21		XP_011520273.1
LOC124903470	XM_047433405.1 link	c.*368T>C	downstream_gene_variant			XP_047289361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6 link	c.-138T>C		5_prime_UTR_variant	Exon 1 of 22	1	NM_003246.4	ENSP00000260356.5		P07996-1
THBS1	ENST00000397591.2 link	c.-259T>C		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000380720.2		A8MZG1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60345

AN:

151996

Hom.:

14591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.280

AC:

164

AN:

586

Hom.:

Cov.:

AF XY:

0.316

AC XY:

100

AN XY:

316

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.264

AC:

110

AN:

416

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.339

AC:

AN:

124

Other (OTH)

AF:

0.313

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.397

AC:

60419

AN:

152112

Hom.:

14620

Cov.:

AF XY:

0.388

AC XY:

28874

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.689

AC:

28606

AN:

41498

American (AMR)

AF:

0.294

AC:

4490

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

944

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1742

AN:

5150

South Asian (SAS)

AF:

0.277

AC:

1335

AN:

4822

European-Finnish (FIN)

AF:

0.215

AC:

2283

AN:

10596

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19889

AN:

67964

Other (OTH)

AF:

0.371

AC:

785

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1657

3313

4970

6626

8283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.316

Hom.:

13663

Bravo

AF:

0.416

Asia WGS

AF:

0.325

AC:

1134

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.7

(source)

DANN

Benign

0.52

PhyloP100

0.24

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=300/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over