Variant rs35410697 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139027.6(ADAMTS13):c.173-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 1,610,810 control chromosomes in the GnomAD database, including 3,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 228 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3021 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.520

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-133424303-C-T is Benign according to our data. Variant chr9-133424303-C-T is described in ClinVar as [Benign]. Clinvar id is 262427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.173-18C>T		intron_variant		ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.173-18C>T		intron_variant		1	NM_139027.6	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6832

AN:

152100

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0711

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0463

AC:

11500

AN:

248498

Hom.:

389

AF XY:

0.0468

AC XY:

6301

AN XY:

134738

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.0430

Gnomad NFE exome

AF:

0.0708

Gnomad OTH exome

AF:

0.0534

GnomAD4 exome

AF:

0.0600

AC:

87483

AN:

1458592

Hom.:

3021

Cov.:

AF XY:

0.0588

AC XY:

42651

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.00996

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.0668

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0180

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0691

Gnomad4 OTH exome

AF:

0.0551

GnomAD4 genome

AF:

0.0449

AC:

6829

AN:

152218

Hom.:

228

Cov.:

AF XY:

0.0436

AC XY:

3245

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0700

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0397

Gnomad4 NFE

AF:

0.0711

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0618

Hom.:

Bravo

AF:

0.0439

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.53

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

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