Variant chr21-26838049-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006988.5(ADAMTS1):c.2434C>T(p.Arg812Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00545 in 1,614,144 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R812H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 39 hom. )

Consequence

ADAMTS1
NM_006988.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

ADAMTS1 (HGNC:217): (ADAM metallopeptidase with thrombospondin type 1 motif 1) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene contains two disintegrin loops and three C-terminal TS motifs and has anti-angiogenic activity. The expression of this gene may be associated with various inflammatory processes as well as development of cancer cachexia. This gene is likely to be necessary for normal growth, fertility, and organ morphology and function. [provided by RefSeq, Jul 2008]

ADAMTS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012444198).

BP6

Variant 21-26838049-G-A is Benign according to our data. Variant chr21-26838049-G-A is described in ClinVar as [Benign]. Clinvar id is 710093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS1	NM_006988.5 linkuse as main transcript	c.2434C>T	p.Arg812Cys	missense_variant	9/9	ENST00000284984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS1	ENST00000284984.8 linkuse as main transcript	c.2434C>T	p.Arg812Cys	missense_variant	9/9	1	NM_006988.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

547

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00669

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00367

AC:

923

AN:

251384

Hom.:

AF XY:

0.00351

AC XY:

477

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00687

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00565

AC:

8258

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

4067

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152276

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00669

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00328

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00368

AC:

447

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00569

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.078

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.020

Polyphen

0.97

Vest4

0.48

MVP

0.57

MPC

1.0

ClinPred

0.033

GERP RS

4.7

Varity_R

0.36

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over