rs34100568

chr9-133454374-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.3045-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,608,612 control chromosomes in the GnomAD database, including 1,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (104 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1680 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.56

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=-0.9).
• BP6: Variant 9-133454374-G-A is Benign according to our data. Variant chr9-133454374-G-A is described in ClinVar as [Benign]. Clinvar id is 262439.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-133454374-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS13	NM_139027.6	c.3045-41G>A		intron_variant		ENST00000355699.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.3045-41G>A		intron_variant		1	NM_139027.6	A2

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4965 AN: 152188 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0324 AC: 8053 AN: 248176 Hom.: 192 AF XY: 0.0333 AC XY: 4485 AN XY: 134740

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0528

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0151

Gnomad FIN exome AF: 0.0176

Gnomad NFE exome AF: 0.0496

Gnomad OTH exome AF: 0.0407

GnomAD4 exome AF: 0.0448 AC: 65264 AN: 1456306 Hom.: 1680 Cov.: 31 AF XY: 0.0438 AC XY: 31745 AN XY: 724838

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.0240

Gnomad4 ASJ exome AF: 0.0506

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0150

Gnomad4 FIN exome AF: 0.0169

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0326 AC: 4962 AN: 152306 Hom.: 104 Cov.: 33 AF XY: 0.0320 AC XY: 2384 AN XY: 74478

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0406 Hom.: 32

Bravo AF: 0.0337

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.12
Dann	Benign	0.56

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: rs34100568; hg19: chr9-136319496;