rs757552302

Variant names:

• chr15-78763735-G-A
• rs757552302
• NM_014272.5:c.4704C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78763735-G-A
• chr15-78763735-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014272.5(ADAMTS7):​c.4704C>T​(p.His1568His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS7 NM_014272.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.404 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS7	NM_014272.5	c.4704C>T	p.His1568His	synonymous_variant	Exon 22 of 24	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1	c.4704C>T	p.His1568His	synonymous_variant	Exon 22 of 24		XP_047288078.1
ADAMTS7	XM_047432123.1	c.3945C>T	p.His1315His	synonymous_variant	Exon 21 of 23		XP_047288079.1
ADAMTS7	XM_011521166.3	c.2958C>T	p.His986His	synonymous_variant	Exon 11 of 13		XP_011519468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS7	ENST00000388820.5	c.4704C>T	p.His1568His	synonymous_variant	Exon 22 of 24	1	NM_014272.5	ENSP00000373472.4
ADAMTS7	ENST00000569934.1	n.*216C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000440 AC: 1 AN: 227422 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125360

Gnomad AFR exome AF: 0.0000723

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2 AN: 1440782 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715254

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.44
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757552302; hg19: chr15-79056077;