Genetic Variant THBS1:c.1121-31C>G (chr15-39587316-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003246.4(THBS1):c.1121-31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

THBS1
NM_003246.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

9 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-IT1 (HGNC:55225): (THBS1 intronic transcript 1)

THBS1-IT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4 link	c.1121-31C>G	intron_variant	Intron 7 of 21	ENST00000260356.6	NP_003237.2	P07996-1
THBS1	XM_047432980.1 link	c.1121-31C>G	intron_variant	Intron 7 of 21		XP_047288936.1
THBS1	XM_011521971.3 link	c.1121-31C>G	intron_variant	Intron 7 of 20		XP_011520273.1
THBS1-IT1	NR_186398.1 link	n.*63C>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
THBS1	ENST00000260356.6 link	c.1121-31C>G	intron_variant	Intron 7 of 21	1	NM_003246.4	ENSP00000260356.5	P07996-1
THBS1	ENST00000466755.1 link	n.-136C>G	upstream_gene_variant		2
THBS1	ENST00000497720.1 link	n.-115C>G	upstream_gene_variant		2
THBS1-IT1	ENST00000478845.2 link	n.*23C>G	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713802

African (AFR)

AF:

0.00

AC:

AN:

33278

American (AMR)

AF:

0.00

AC:

AN:

43948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25096

East Asian (EAS)

AF:

0.00

AC:

AN:

39384

South Asian (SAS)

AF:

0.00

AC:

AN:

83430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098970

Other (OTH)

AF:

0.00

AC:

AN:

59628

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2018

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.044

(source)

DANN

Benign

0.47

PhyloP100

-2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over