Variant rs36023469 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.3045-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,604,582 control chromosomes in the GnomAD database, including 1,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 104 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1676 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.13

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=-0.92).

BP6

Variant 9-133454367-T-C is Benign according to our data. Variant chr9-133454367-T-C is described in ClinVar as [Benign]. Clinvar id is 262440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454367-T-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.3045-48T>C		intron_variant		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.3045-48T>C		intron_variant		1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4965

AN:

152172

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0324

AC:

8042

AN:

247840

Hom.:

190

AF XY:

0.0333

AC XY:

4488

AN XY:

134640

show subpopulations

Gnomad AFR exome

AF:

0.00923

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0527

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.0176

Gnomad NFE exome

AF:

0.0497

Gnomad OTH exome

AF:

0.0407

GnomAD4 exome

AF:

0.0448

AC:

65108

AN:

1452292

Hom.:

1676

Cov.:

AF XY:

0.0438

AC XY:

31687

AN XY:

723160

show subpopulations

Gnomad4 AFR exome

AF:

0.00820

Gnomad4 AMR exome

AF:

0.0240

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0170

Gnomad4 NFE exome

AF:

0.0520

Gnomad4 OTH exome

AF:

0.0413

GnomAD4 genome

AF:

0.0326

AC:

4962

AN:

152290

Hom.:

104

Cov.:

AF XY:

0.0320

AC XY:

2382

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0407

Hom.:

Bravo

AF:

0.0337

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

DANN

Benign

0.38

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