rs2285489

chr9-133424254-T-Cchr9-133424254-T-G

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.173-67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,601,052 control chromosomes in the GnomAD database, including 327,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35606 hom., cov: 31)
  • Exomes 𝑓: 0.63 (291921 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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=-1.0).
• BP6: Variant 9-133424254-T-C is Benign according to our data. Variant chr9-133424254-T-C is described in ClinVar as [Benign]. Clinvar id is 1221388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.173-67T>C		intron_variant		ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.173-67T>C		intron_variant		1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103067 AN: 151806 Hom.: 35562 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.631 AC: 914860 AN: 1449128 Hom.: 291921 AF XY: 0.629 AC XY: 453762 AN XY: 721286

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.639

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.679 AC: 103165 AN: 151924 Hom.: 35606 Cov.: 31 AF XY: 0.676 AC XY: 50188 AN XY: 74246

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.717

Alfa AF: 0.643 Hom.: 4291

Bravo AF: 0.699

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-1.0
Cadd	Benign	0.61
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs2285489; hg19: chr9-136289374; COSMIC: COSV63020635;