chr15-78796769-A-G

Position:

• chr15-78796769-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 15/20 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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ADAMTS7	NM_014272.5	c.640T>C	p.Ser214Pro	missense_variant	4/24	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1	c.640T>C	p.Ser214Pro	missense_variant	4/24		XP_047288078.1
ADAMTS7	XM_047432123.1	c.-120T>C		5_prime_UTR_variant	3/23		XP_047288079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS7	ENST00000388820.5	c.640T>C	p.Ser214Pro	missense_variant	4/24	1	NM_014272.5	ENSP00000373472.4
ADAMTS7	ENST00000565793.5	n.537T>C		non_coding_transcript_exon_variant	3/12	2
ADAMTS7	ENST00000566303.5	n.703T>C		non_coding_transcript_exon_variant	4/10	5
ADAMTS7	ENST00000568712.1	n.652T>C		non_coding_transcript_exon_variant	4/15	2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49910 AN: 151812 Hom.: 9421 Cov.: 33

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

GnomAD3 exomes AF: 0.343 AC: 83889 AN: 244334 Hom.: 16022 AF XY: 0.356 AC XY: 47258 AN XY: 132686

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 SAS exome AF: 0.345

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.: 53 AF XY: 0.410 AC XY: 297652 AN XY: 725104

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.329 AC: 49926 AN: 151930 Hom.: 9423 Cov.: 33 AF XY: 0.324 AC XY: 24025 AN XY: 74228

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.355

Alfa AF: 0.418 Hom.: 8389

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

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.19
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.036	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.14	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.042
Sift	Benign	0.39	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.24
ClinPred		0.98	D
GERP RS		-9.0
Varity_R		0.030
gMVP		0.47

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

Other links and lift over

dbSNP: rs3825807; hg19: chr15-79089111; COSMIC: COSV66306379;