15-78763726-C-A

Variant names:

• chr15-78763726-C-A
• rs188808047
• NM_014272.5:c.4713G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014272.5(ADAMTS7):​c.4713G>T​(p.Thr1571Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,566,394 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (16 hom., cov: 34)
  • Exomes 𝑓: 0.0057 (54 hom.)
• Consequence: ADAMTS7 NM_014272.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-78763726-C-A is Benign according to our data. Variant chr15-78763726-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2645614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	NM_014272.5	MANE Select	c.4713G>T	p.Thr1571Thr	synonymous	Exon 22 of 24	NP_055087.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS7	ENST00000388820.5	TSL:1 MANE Select	c.4713G>T	p.Thr1571Thr	synonymous	Exon 22 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4686G>T	p.Thr1562Thr	synonymous	Exon 22 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4713G>T	p.Thr1571Thr	synonymous	Exon 22 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 1039 AN: 152256 Hom.: 16 Cov.: 34

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00807

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00610 AC: 1299 AN: 213010 AF XY: 0.00590

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.000383

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0343

Gnomad NFE exome AF: 0.00704

Gnomad OTH exome AF: 0.00686

GnomAD4 exome AF: 0.00568 AC: 8027 AN: 1414020 Hom.: 54 Cov.: 31 AF XY: 0.00553 AC XY: 3862 AN XY: 698638

African (AFR) AF: 0.000803 AC: 26 AN: 32392

American (AMR) AF: 0.00199 AC: 80 AN: 40200

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 28 AN: 24192

East Asian (EAS) AF: 0.00 AC: 0 AN: 38998

South Asian (SAS) AF: 0.000560 AC: 46 AN: 82162

European-Finnish (FIN) AF: 0.0307 AC: 1366 AN: 44506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3982

European-Non Finnish (NFE) AF: 0.00567 AC: 6177 AN: 1089370

Other (OTH) AF: 0.00522 AC: 304 AN: 58218

GnomAD4 genome AF: 0.00682 AC: 1039 AN: 152374 Hom.: 16 Cov.: 34 AF XY: 0.00833 AC XY: 621 AN XY: 74508

African (AFR) AF: 0.000769 AC: 32 AN: 41596

American (AMR) AF: 0.00131 AC: 20 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0398 AC: 423 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00807 AC: 549 AN: 68032

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00959 Hom.: 3

Bravo AF: 0.00319

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.024
DANN	Benign	0.78
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs188808047; hg19: chr15-79056068; COSMIC: COSV104429362; COSMIC: COSV104429362;