rs150570920

Variant names:

• chr15-78762415-C-T
• rs150570920
• NM_014272.5:c.4891G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78762415-C-T
• chr15-78762415-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014272.5(ADAMTS7):​c.4891G>A​(p.Val1631Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,488,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ADAMTS7 NM_014272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.124
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013550401).

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.4891G>A	p.Val1631Ile	missense	Exon 23 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.4891G>A	p.Val1631Ile	missense	Exon 23 of 24	ENSP00000373472.4	Q9UKP4
	ADAMTS7	ENST00000972106.1		c.4864G>A	p.Val1622Ile	missense	Exon 23 of 24	ENSP00000642165.1
	ADAMTS7	ENST00000972107.1		c.4831G>A	p.Val1611Ile	missense	Exon 23 of 24	ENSP00000642166.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000291 AC: 4 AN: 137612 AF XY: 0.0000135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000532

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000942

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000160

Gnomad OTH exome AF: 0.000324

GnomAD4 exome AF: 0.0000202 AC: 27 AN: 1336442 Hom.: 0 Cov.: 30 AF XY: 0.0000198 AC XY: 13 AN XY: 657182

African (AFR) AF: 0.0000350 AC: 1 AN: 28592

American (AMR) AF: 0.000204 AC: 6 AN: 29484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20374

East Asian (EAS) AF: 0.0000593 AC: 2 AN: 33714

South Asian (SAS) AF: 0.0000146 AC: 1 AN: 68692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 0.00000763 AC: 8 AN: 1048624

Other (OTH) AF: 0.000165 AC: 9 AN: 54582

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000268 AC XY: 20 AN XY: 74494

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.00216 AC: 33 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000540

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.51
DANN	Benign	0.78
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.12
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.029
Sift	Benign	0.52	T
Sift4G	Benign	0.21	T
Polyphen		0.0040	B
Vest4		0.065
MutPred		0.21		Loss of glycosylation at P1633 (P = 0.5633)
MVP		0.16
MPC		0.13
ClinPred		0.014	T
GERP RS		-8.2
Varity_R		0.018
gMVP		0.10
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150570920; hg19: chr15-79054757; COSMIC: COSV105321629; COSMIC: COSV105321629;