rs34100568

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.56

Publications

1 publications found

Variant links:

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)

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133454374-G-A is described in CliVar as Benign. Clinvar id is 262439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 link	c.3045-41G>A		intron_variant	Intron 23 of 28	ENST00000355699.7	NP_620596.2	Q76LX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 link	c.3045-41G>A		intron_variant	Intron 23 of 28	1	NM_139027.6	ENSP00000347927.2		Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4965

AN:

152188

Hom.:

105

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0324

AC:

8053

AN:

248176

AF XY:

0.0333

show subpopulations

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 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.:

AF XY:

0.0438

AC XY:

31745

AN XY:

724838

show subpopulations

African (AFR)

AF:

0.00824

AC:

275

AN:

33372

American (AMR)

AF:

0.0240

AC:

1072

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0506

AC:

1322

AN:

26106

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39654

South Asian (SAS)

AF:

0.0150

AC:

1294

AN:

86044

European-Finnish (FIN)

AF:

0.0169

AC:

886

AN:

52278

Middle Eastern (MID)

AF:

0.0493

AC:

284

AN:

5760

European-Non Finnish (NFE)

AF:

0.0520

AC:

57648

AN:

1108128

Other (OTH)

AF:

0.0412

AC:

2481

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3325

6649

9974

13298

16623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2148

4296

6444

8592

10740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0326

AC:

4962

AN:

152306

Hom.:

104

Cov.:

AF XY:

0.0320

AC XY:

2384

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0100

AC:

416

AN:

41566

American (AMR)

AF:

0.0374

AC:

572

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

183

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0197

AC:

209

AN:

10626

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0498

AC:

3388

AN:

68014

Other (OTH)

AF:

0.0403

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

257

514

771

1028

1285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0407

Hom.:

Bravo

AF:

0.0337

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

(source)

DANN

Benign

0.56

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over