rs1994016

Variant names:

• chr15-78787892-C-T
• rs1994016
• NM_014272.5:c.1322+339G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014272.5(ADAMTS7):​c.1322+339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,962 control chromosomes in the GnomAD database, including 8,123 homozygotes. 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: 𝑓 0.30 (8123 hom., cov: 31)
• Consequence: ADAMTS7 NM_014272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 65 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS7	NM_014272.5	c.1322+339G>A		intron_variant	Intron 8 of 23	ENST00000388820.5	NP_055087.2
ADAMTS7	XM_047432122.1	c.1322+339G>A		intron_variant	Intron 8 of 23		XP_047288078.1
ADAMTS7	XM_047432123.1	c.563+339G>A		intron_variant	Intron 7 of 22		XP_047288079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS7	ENST00000388820.5	c.1322+339G>A		intron_variant	Intron 8 of 23	1	NM_014272.5	ENSP00000373472.4
ADAMTS7	ENST00000565793.5	n.1219+339G>A		intron_variant	Intron 7 of 11	2
ADAMTS7	ENST00000566303.5	n.1309+339G>A		intron_variant	Intron 8 of 9	5
ADAMTS7	ENST00000568712.1	n.1334+339G>A		intron_variant	Intron 8 of 14	2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45875 AN: 151844 Hom.: 8120 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45879 AN: 151962 Hom.: 8123 Cov.: 31 AF XY: 0.296 AC XY: 21958 AN XY: 74284

African (AFR) AF: 0.136 AC: 5626 AN: 41456

American (AMR) AF: 0.281 AC: 4294 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1317 AN: 3472

East Asian (EAS) AF: 0.0867 AC: 448 AN: 5166

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3306 AN: 10546

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28357 AN: 67926

Other (OTH) AF: 0.322 AC: 676 AN: 2102

Alfa AF: 0.358 Hom.: 11696

Bravo AF: 0.292

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1994016; hg19: chr15-79080234;