rs652600

chr9-133445896-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139027.6(ADAMTS13):c.2731+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,500,210 control chromosomes in the GnomAD database, including 355,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33504 hom., cov: 32)
  • Exomes 𝑓: 0.68 (321530 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.247

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-133445896-G-A is Benign according to our data. Variant chr9-133445896-G-A is described in ClinVar as [Benign]. Clinvar id is 812619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.2731+77G>A		intron_variant		ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.2731+77G>A		intron_variant		1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99240 AN: 151968 Hom.: 33468 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.642

GnomAD4 exome AF: 0.684 AC: 921726 AN: 1348124 Hom.: 321530 AF XY: 0.682 AC XY: 449389 AN XY: 658514

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.808

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.653 AC: 99318 AN: 152086 Hom.: 33504 Cov.: 32 AF XY: 0.653 AC XY: 48521 AN XY: 74350

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.637

Alfa AF: 0.683 Hom.: 28616

Bravo AF: 0.629

Asia WGS AF: 0.450 AC: 1568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.081
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs652600; hg19: chr9-136311017; COSMIC: COSV63021038;