9-133421761-G-A

Position:

• chr9-133421761-G-A

Variant summary

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

The ENST00000485925.5(ADAMTS13):​n.288-1340G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,270 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.055 (330 hom., cov: 32)
• Consequence: ADAMTS13 ENST00000485925.5 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.280

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=-0.82).
• BP6: Variant 9-133421761-G-A is Benign according to our data. Variant chr9-133421761-G-A is described in ClinVar as [Benign]. Clinvar id is 1288910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	XM_017014232.2	c.-125G>A		5_prime_UTR_variant	1/29
ADAMTS13	XM_017014233.2	c.-285-1340G>A		intron_variant
ADAMTS13	NR_024514.3	n.309-1340G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000485925.5	n.288-1340G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8340 AN: 152152 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0547 AC: 8336 AN: 152270 Hom.: 330 Cov.: 32 AF XY: 0.0535 AC XY: 3986 AN XY: 74468

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0732 Hom.: 51

Bravo AF: 0.0535

Asia WGS AF: 0.0150 AC: 51 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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34785487; hg19: chr9-136286881; COSMIC: COSV63020618;