Variant chr1-161191082-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005099.6(ADAMTS4):c.*56A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,496,092 control chromosomes in the GnomAD database, including 18,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1641 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16653 hom. )

Consequence

ADAMTS4
NM_005099.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.230

Variant links:

Genes affected

ADAMTS4 (HGNC:220): (ADAM metallopeptidase with thrombospondin type 1 motif 4) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of this 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 enzyme encoded by this gene lacks a C-terminal TS motif. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The expression of this gene is upregulated in arthritic disease and this may contribute to disease progression through the degradation of aggrecan. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ADAMTS4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-161191082-T-C is Benign according to our data. Variant chr1-161191082-T-C is described in ClinVar as [Benign]. Clinvar id is 769539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS4	NM_005099.6 linkuse as main transcript	c.*56A>G		3_prime_UTR_variant	9/9	ENST00000367996.6
ADAMTS4	NM_001320336.3 linkuse as main transcript	c.2409A>G	p.Arg803=	synonymous_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS4	ENST00000367996.6 linkuse as main transcript	c.*56A>G		3_prime_UTR_variant	9/9	1	NM_005099.6	P1	O75173-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19731

AN:

152126

Hom.:

1643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.150

AC:

201028

AN:

1343846

Hom.:

16653

Cov.:

AF XY:

0.149

AC XY:

98063

AN XY:

657926

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.130

AC:

19725

AN:

152246

Hom.:

1641

Cov.:

AF XY:

0.131

AC XY:

9748

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0453

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.341

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.138

Hom.:

307

Bravo

AF:

0.134

Asia WGS

AF:

0.208

AC:

724

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.2

DANN

Benign

0.71

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