Variant rs28641026 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000355699.7(ADAMTS13):c.2910C>T(p.Val970=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,613,948 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 104 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1240 hom. )

Consequence

ADAMTS13
ENST00000355699.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.14

Variant links:

Genes affected

ADAMTS13 (HGNC:1366): (ADAM metallopeptidase with thrombospondin type 1 motif 13) This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ADAMTS13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-133449831-C-T is Benign according to our data. Variant chr9-133449831-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133449831-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0308 (4694/152198) while in subpopulation NFE AF= 0.0403 (2742/67996). AF 95% confidence interval is 0.0391. There are 104 homozygotes in gnomad4. There are 2366 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 104 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.2910C>T	p.Val970=	synonymous_variant	23/29	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.2910C>T	p.Val970=	synonymous_variant	23/29	1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4692

AN:

152080

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.0723

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0403

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0313

AC:

7850

AN:

250634

Hom.:

167

AF XY:

0.0324

AC XY:

4398

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0227

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.0675

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0376

AC:

54923

AN:

1461750

Hom.:

1240

Cov.:

AF XY:

0.0372

AC XY:

27065

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00980

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0229

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.0308

AC:

4694

AN:

152198

Hom.:

104

Cov.:

AF XY:

0.0318

AC XY:

2366

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.0723

Gnomad4 NFE

AF:

0.0403

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.0343

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0379

EpiControl

AF:

0.0370

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2020	This variant is associated with the following publications: (PMID: 22768050) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Upshaw-Schulman syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.27

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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