rs4962153

Positions:

• chr9-133458632-A-G
• chr9-133458632-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_139027.6(ADAMTS13):​c.3910-342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 148,890 control chromosomes in the GnomAD database, including 48,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.80 (48042 hom., cov: 25)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.290

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-133458632-A-G is Benign according to our data. Variant chr9-133458632-A-G is described in ClinVar as [Benign]. Clinvar id is 812620.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.3910-342A>G		intron_variant		ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.3910-342A>G		intron_variant		1	NM_139027.6	ENSP00000347927	A2

Frequencies

GnomAD3 genomes AF: 0.798 AC: 118724 AN: 148778 Hom.: 47991 Cov.: 25

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.798 AC: 118834 AN: 148890 Hom.: 48042 Cov.: 25 AF XY: 0.801 AC XY: 57819 AN XY: 72192

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.806

Alfa AF: 0.835 Hom.: 67858

Bravo AF: 0.793

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs4962153; hg19: chr9-136323754;