rs4962153

Variant names:

• chr9-133458632-A-G
• rs4962153
• NM_139027.6:c.3910-342A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 publications found

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 Gene-Disease associations (from GenCC):

• congenital thrombotic thrombocytopenic purpura

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS13	NM_139027.6	MANE Select	c.3910-342A>G		intron	N/A	NP_620596.2	Q76LX8-2
	ADAMTS13	NM_139025.5		c.4078-342A>G		intron	N/A	NP_620594.1	Q76LX8-1
	ADAMTS13	NM_139026.6		c.3817-342A>G		intron	N/A	NP_620595.1	Q76LX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS13	ENST00000355699.7	TSL:1 MANE Select	c.3910-342A>G		intron	N/A	ENSP00000347927.2	Q76LX8-2
	ADAMTS13	ENST00000371929.7	TSL:1	c.4078-342A>G		intron	N/A	ENSP00000360997.3	Q76LX8-1
	ADAMTS13	ENST00000356589.6	TSL:1	c.3817-342A>G		intron	N/A	ENSP00000348997.2	Q76LX8-3

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

African (AFR) AF: 0.669 AC: 26983 AN: 40338

American (AMR) AF: 0.850 AC: 12573 AN: 14798

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2559 AN: 3468

East Asian (EAS) AF: 0.930 AC: 4691 AN: 5044

South Asian (SAS) AF: 0.873 AC: 4131 AN: 4730

European-Finnish (FIN) AF: 0.821 AC: 7804 AN: 9506

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57619 AN: 67726

Other (OTH) AF: 0.806 AC: 1679 AN: 2084

Alfa AF: 0.831 Hom.: 193180

Bravo AF: 0.793

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4962153; hg19: chr9-136323754;