15-78763780-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014272.5(ADAMTS7):c.4659C>T(p.Cys1553=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,593,752 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0017 (16 hom.)
• Consequence: ADAMTS7 NM_014272.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-78763780-G-A is Benign according to our data. Variant chr15-78763780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS7	NM_014272.5	c.4659C>T	p.Cys1553=	synonymous_variant	22/24	ENST00000388820.5
ADAMTS7	XM_047432122.1	c.4659C>T	p.Cys1553=	synonymous_variant	22/24
ADAMTS7	XM_047432123.1	c.3900C>T	p.Cys1300=	synonymous_variant	21/23
ADAMTS7	XM_011521166.3	c.2913C>T	p.Cys971=	synonymous_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS7	ENST00000388820.5	c.4659C>T	p.Cys1553=	synonymous_variant	22/24	1	NM_014272.5	P1

Frequencies

GnomAD3 genomes AF: 0.00128 AC: 195 AN: 152212 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00209 AC: 446 AN: 213560 Hom.: 5 AF XY: 0.00246 AC XY: 287 AN XY: 116850

Gnomad AFR exome AF: 0.0000783

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00404

Gnomad EAS exome AF: 0.0000608

Gnomad SAS exome AF: 0.00729

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.00192

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00167 AC: 2401 AN: 1441422 Hom.: 16 Cov.: 31 AF XY: 0.00191 AC XY: 1364 AN XY: 715788

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000421

Gnomad4 ASJ exome AF: 0.00420

Gnomad4 EAS exome AF: 0.0000766

Gnomad4 SAS exome AF: 0.00749

Gnomad4 FIN exome AF: 0.000457

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome AF: 0.00128 AC: 195 AN: 152330 Hom.: 0 Cov.: 34 AF XY: 0.00142 AC XY: 106 AN XY: 74498

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00848

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00172

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00202 Hom.: 0

Bravo AF: 0.00102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	ADAMTS7: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	2.9
Dann	Benign	0.56

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: rs112320482; hg19: chr15-79056122; COSMIC: COSV104429393; COSMIC: COSV104429393;