chr9-133439859-A-T

Variant names:

• chr9-133439859-A-T
• rs139789731
• NM_139027.6:c.1786+413A>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_139027.6(ADAMTS13):​c.1786+413A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 152,272 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0046 (1 hom., cov: 33)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00462 (704/152272) while in subpopulation NFE AF= 0.00726 (494/68016). AF 95% confidence interval is 0.00673. There are 1 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6	c.1786+413A>T		intron_variant	Intron 15 of 28	ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7	c.1786+413A>T		intron_variant	Intron 15 of 28	1	NM_139027.6	ENSP00000347927.2

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 704 AN: 152154 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00726

Gnomad OTH AF: 0.00430

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

GnomAD4 genome AF: 0.00462 AC: 704 AN: 152272 Hom.: 1 Cov.: 33 AF XY: 0.00428 AC XY: 319 AN XY: 74476

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00581

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00726

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.00492

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.032
DANN	Benign	0.46

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: rs139789731; hg19: chr9-136304980;