rs28729234

Variant names:

• chr9-133430112-C-T
• rs28729234
• NM_139027.6:c.987+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133430112-C-T
• chr9-133430112-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139027.6(ADAMTS13):​c.987+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,571,394 control chromosomes in the GnomAD database, including 10,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (741 hom., cov: 30)
  • Exomes 𝑓: 0.11 (9786 hom.)
• Consequence: ADAMTS13 NM_139027.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.384
• Publications: 4 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: Genomics England PanelApp, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-133430112-C-T is Benign according to our data. Variant chr9-133430112-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 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.987+11C>T		intron	N/A	NP_620596.2	Q76LX8-2
	ADAMTS13	NM_139025.5		c.987+11C>T		intron	N/A	NP_620594.1	Q76LX8-1
	ADAMTS13	NM_139026.6		c.894+11C>T		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.987+11C>T		intron	N/A	ENSP00000347927.2	Q76LX8-2
	ADAMTS13	ENST00000371929.7	TSL:1	c.987+11C>T		intron	N/A	ENSP00000360997.3	Q76LX8-1
	ADAMTS13	ENST00000356589.6	TSL:1	c.894+11C>T		intron	N/A	ENSP00000348997.2	Q76LX8-3

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13575 AN: 152188 Hom.: 742 Cov.: 30

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0869

GnomAD2 exomes AF: 0.0850 AC: 15251 AN: 179412 AF XY: 0.0866

Gnomad AFR exome AF: 0.0393

Gnomad AMR exome AF: 0.0493

Gnomad ASJ exome AF: 0.0942

Gnomad EAS exome AF: 0.000270

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.0935

GnomAD4 exome AF: 0.111 AC: 157759 AN: 1419088 Hom.: 9786 Cov.: 33 AF XY: 0.109 AC XY: 76635 AN XY: 703796

African (AFR) AF: 0.0375 AC: 1235 AN: 32944

American (AMR) AF: 0.0497 AC: 2053 AN: 41274

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 2334 AN: 25558

East Asian (EAS) AF: 0.000130 AC: 5 AN: 38368

South Asian (SAS) AF: 0.0416 AC: 3436 AN: 82656

European-Finnish (FIN) AF: 0.124 AC: 4696 AN: 37862

Middle Eastern (MID) AF: 0.0930 AC: 529 AN: 5688

European-Non Finnish (NFE) AF: 0.126 AC: 137713 AN: 1095744

Other (OTH) AF: 0.0976 AC: 5758 AN: 58994

GnomAD4 genome AF: 0.0891 AC: 13574 AN: 152306 Hom.: 741 Cov.: 30 AF XY: 0.0891 AC XY: 6633 AN XY: 74466

African (AFR) AF: 0.0407 AC: 1692 AN: 41570

American (AMR) AF: 0.0720 AC: 1103 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4832

European-Finnish (FIN) AF: 0.129 AC: 1373 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8559 AN: 68016

Other (OTH) AF: 0.0855 AC: 181 AN: 2116

Alfa AF: 0.107 Hom.: 188

Bravo AF: 0.0833

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Upshaw-Schulman syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.85
PhyloP100		-0.38
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

Other links and lift over

dbSNP: rs28729234; hg19: chr9-136295232; COSMIC: COSV107438271; COSMIC: COSV107438271;