chr15-78796769-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014272.5(ADAMTS7):c.640T>C(p.Ser214Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,609,266 control chromosomes in the GnomAD database, including 137,567 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 (★).

Frequency

Genomes: 𝑓 0.33 ( 9423 hom., cov: 33)

Exomes 𝑓: 0.41 ( 128144 hom. )

Consequence

ADAMTS7
NM_014272.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.04

Publications

151 publications found

Variant links:

Genes affected

ADAMTS7 (HGNC:223): (ADAM metallopeptidase with thrombospondin type 1 motif 7) The protein encoded by this gene is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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 encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and may regulate vascular smooth muscle cell (VSMC) migration. Mutations in this gene may be associated with susceptibility to coronary artery disease. [provided by RefSeq, Feb 2016]

ADAMTS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5765429E-4).

BP6

Variant 15-78796769-A-G is Benign according to our data. Variant chr15-78796769-A-G is described in ClinVar as Benign. ClinVar VariationId is 812638.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ADAMTS7	NM_014272.5 link	c.640T>C	p.Ser214Pro	missense_variant	Exon 4 of 24	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1 link	c.640T>C	p.Ser214Pro	missense_variant	Exon 4 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1 link	c.-120T>C		5_prime_UTR_variant	Exon 3 of 23		XP_047288079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ADAMTS7	ENST00000388820.5 link	c.640T>C	p.Ser214Pro	missense_variant	Exon 4 of 24	1	NM_014272.5	ENSP00000373472.4
ADAMTS7	ENST00000565793.5 link	n.537T>C		non_coding_transcript_exon_variant	Exon 3 of 12	2
ADAMTS7	ENST00000566303.5 link	n.703T>C		non_coding_transcript_exon_variant	Exon 4 of 10	5
ADAMTS7	ENST00000568712.1 link	n.652T>C		non_coding_transcript_exon_variant	Exon 4 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

49910

AN:

151812

Hom.:

9421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.358

GnomAD2 exomes

AF:

0.343

AC:

83889

AN:

244334

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.411

AC:

599236

AN:

1457336

Hom.:

128144

Cov.:

AF XY:

0.410

AC XY:

297652

AN XY:

725104

show subpopulations

African (AFR)

AF:

0.146

AC:

4885

AN:

33464

American (AMR)

AF:

0.226

AC:

10042

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10453

AN:

26100

East Asian (EAS)

AF:

0.140

AC:

5550

AN:

39682

South Asian (SAS)

AF:

0.349

AC:

30061

AN:

86142

European-Finnish (FIN)

AF:

0.342

AC:

17154

AN:

50200

Middle Eastern (MID)

AF:

0.424

AC:

2413

AN:

5688

European-Non Finnish (NFE)

AF:

0.446

AC:

495154

AN:

1111208

Other (OTH)

AF:

0.390

AC:

23524

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18859

37718

56577

75436

94295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14630

29260

43890

58520

73150

<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:

0.329

AC:

49926

AN:

151930

Hom.:

9423

Cov.:

AF XY:

0.324

AC XY:

24025

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.156

AC:

6479

AN:

41466

American (AMR)

AF:

0.305

AC:

4647

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1395

AN:

3466

East Asian (EAS)

AF:

0.150

AC:

773

AN:

5144

South Asian (SAS)

AF:

0.338

AC:

1623

AN:

4806

European-Finnish (FIN)

AF:

0.346

AC:

3647

AN:

10532

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.443

AC:

30111

AN:

67952

Other (OTH)

AF:

0.355

AC:

748

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1662

3325

4987

6650

8312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.402

Hom.:

26206

Bravo

AF:

0.316

TwinsUK

AF:

0.441

AC:

1635

ALSPAC

AF:

0.453

AC:

1746

ESP6500AA

AF:

0.154

AC:

678

ESP6500EA

AF:

0.445

AC:

3816

ExAC

AF:

0.345

AC:

41830

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:Benign

Review Status:no assertion criteria provided

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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.19

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.011

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.036

MetaRNN

Benign

0.00016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.14

PhyloP100

-2.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.080

REVEL

Benign

0.042

Sift

Benign

0.39

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.034

MPC

0.24

ClinPred

0.98

GERP RS

-9.0

Varity_R

0.030

gMVP

0.47

Mutation Taster

=99/1

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