Variant rs35194094 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.173-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,605,832 control chromosomes in the GnomAD database, including 4,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 325 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4551 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 9-133424273-G-A is Benign according to our data. Variant chr9-133424273-G-A is described in ClinVar as [Benign]. Clinvar id is 262428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.173-48G>A		intron_variant		ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 link	c.173-48G>A		intron_variant		1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8334

AN:

152002

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0478

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0547

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0866

Gnomad OTH

AF:

0.0556

GnomAD3 exomes

AF:

0.0560

AC:

13661

AN:

243800

Hom.:

560

AF XY:

0.0568

AC XY:

7535

AN XY:

132774

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0336

Gnomad ASJ exome

AF:

0.0714

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.0546

Gnomad NFE exome

AF:

0.0868

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0741

AC:

107742

AN:

1453712

Hom.:

4551

Cov.:

AF XY:

0.0724

AC XY:

52397

AN XY:

723446

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.0349

Gnomad4 ASJ exome

AF:

0.0696

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0547

Gnomad4 NFE exome

AF:

0.0858

Gnomad4 OTH exome

AF:

0.0666

GnomAD4 genome

AF:

0.0548

AC:

8330

AN:

152120

Hom.:

325

Cov.:

AF XY:

0.0535

AC XY:

3975

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0478

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0547

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.0546

Alfa

AF:

0.0728

Hom.:

Bravo

AF:

0.0534

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.97

CADD

Benign

0.013

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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