rs4747096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_080722.4(ADAMTS14):c.3146A>G(p.Glu1049Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,734 control chromosomes in the GnomAD database, including 27,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. E1049D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.19 ( 2801 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24808 hom. )

Consequence

ADAMTS14
NM_080722.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

Publications

42 publications found

Variant links:

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) 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 encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ADAMTS14 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 (MetaRNN=0.004669875).

BP6

Variant 10-70758253-A-G is Benign according to our data. Variant chr10-70758253-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4 link	c.3146A>G	p.Glu1049Gly	missense_variant	Exon 21 of 22	ENST00000373207.2	NP_542453.2	Q8WXS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 link	c.3146A>G	p.Glu1049Gly	missense_variant	Exon 21 of 22	1	NM_080722.4	ENSP00000362303.1		Q8WXS8-1
ADAMTS14	ENST00000373208.5 link	c.3155A>G	p.Glu1052Gly	missense_variant	Exon 21 of 22	2		ENSP00000362304.1		Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28622

AN:

152084

Hom.:

2803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.178

GnomAD2 exomes

AF:

0.192

AC:

48305

AN:

251106

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.179

AC:

262019

AN:

1461532

Hom.:

24808

Cov.:

AF XY:

0.178

AC XY:

129417

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.185

AC:

6177

AN:

33476

American (AMR)

AF:

0.228

AC:

10191

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2816

AN:

26132

East Asian (EAS)

AF:

0.380

AC:

15086

AN:

39694

South Asian (SAS)

AF:

0.146

AC:

12562

AN:

86236

European-Finnish (FIN)

AF:

0.234

AC:

12487

AN:

53380

Middle Eastern (MID)

AF:

0.142

AC:

820

AN:

5766

European-Non Finnish (NFE)

AF:

0.172

AC:

191065

AN:

1111774

Other (OTH)

AF:

0.179

AC:

10815

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

11345

22690

34036

45381

56726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6926

13852

20778

27704

34630

<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:

0.188

AC:

28622

AN:

152202

Hom.:

2801

Cov.:

AF XY:

0.191

AC XY:

14213

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.186

AC:

7713

AN:

41534

American (AMR)

AF:

0.210

AC:

3219

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3470

East Asian (EAS)

AF:

0.369

AC:

1907

AN:

5174

South Asian (SAS)

AF:

0.148

AC:

716

AN:

4826

European-Finnish (FIN)

AF:

0.238

AC:

2523

AN:

10592

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11582

AN:

67984

Other (OTH)

AF:

0.180

AC:

380

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1187

2373

3560

4746

5933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.172

Hom.:

7431

Bravo

AF:

0.187

TwinsUK

AF:

0.166

AC:

617

ALSPAC

AF:

0.173

AC:

665

ESP6500AA

AF:

0.188

AC:

830

ESP6500EA

AF:

0.161

AC:

1387

ExAC

AF:

0.189

AC:

22882

Asia WGS

AF:

0.268

AC:

934

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23491141) -

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

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.8

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.0085

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.059

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.7

.;N

PhyloP100

1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.059

Sift

Benign

0.67

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.0

.;B

Vest4

0.028

MPC

0.20

ClinPred

0.0012

GERP RS

3.0

Varity_R

0.029

gMVP

0.38

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