Variant rs9406328 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003247.5(THBS2):c.1478-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,598,004 control chromosomes in the GnomAD database, including 107,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8435 hom., cov: 33)

Exomes 𝑓: 0.37 ( 98824 hom. )

Consequence

THBS2
NM_003247.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002656

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.523

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 6-169234915-G-A is Benign according to our data. Variant chr6-169234915-G-A is described in ClinVar as [Benign]. Clinvar id is 12713.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5 linkuse as main transcript	c.1478-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000617924.6
THBS2-AS1	NR_134621.1 linkuse as main transcript	n.682-4310G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6 linkuse as main transcript	c.1478-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1 linkuse as main transcript	n.640-4310G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48335

AN:

151908

Hom.:

8442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.369

AC:

88720

AN:

240332

Hom.:

16983

AF XY:

0.372

AC XY:

48569

AN XY:

130584

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.447

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.365

AC:

528130

AN:

1445978

Hom.:

98824

Cov.:

AF XY:

0.368

AC XY:

264145

AN XY:

717432

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.318

AC:

48334

AN:

152026

Hom.:

8435

Cov.:

AF XY:

0.319

AC XY:

23689

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.341

Hom.:

2993

Bravo

AF:

0.318

Asia WGS

AF:

0.439

AC:

1528

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

THBS2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

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). -

Lumbar disk herniation, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.018

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