Menu
GeneBe

15-78764004-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_014272.5(ADAMTS7):c.4515C>T(p.Pro1505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,543,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

ADAMTS7
NM_014272.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.25
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-78764004-G-A is Benign according to our data. Variant chr15-78764004-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645615.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.25 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTS7NM_014272.5 linkuse as main transcriptc.4515C>T p.Pro1505= synonymous_variant 21/24 ENST00000388820.5
ADAMTS7XM_047432122.1 linkuse as main transcriptc.4515C>T p.Pro1505= synonymous_variant 21/24
ADAMTS7XM_047432123.1 linkuse as main transcriptc.3756C>T p.Pro1252= synonymous_variant 20/23
ADAMTS7XM_011521166.3 linkuse as main transcriptc.2769C>T p.Pro923= synonymous_variant 10/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTS7ENST00000388820.5 linkuse as main transcriptc.4515C>T p.Pro1505= synonymous_variant 21/241 NM_014272.5 P1
ADAMTS7ENST00000569934.1 linkuse as main transcriptn.655C>T non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000670
AC:
102
AN:
152248
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00200
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000251
AC:
38
AN:
151580
Hom.:
0
AF XY:
0.000261
AC XY:
21
AN XY:
80570
show subpopulations
Gnomad AFR exome
AF:
0.00196
Gnomad AMR exome
AF:
0.000124
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000139
Gnomad FIN exome
AF:
0.0000670
Gnomad NFE exome
AF:
0.000240
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000308
AC:
429
AN:
1391232
Hom.:
1
Cov.:
31
AF XY:
0.000314
AC XY:
215
AN XY:
685082
show subpopulations
Gnomad4 AFR exome
AF:
0.00216
Gnomad4 AMR exome
AF:
0.000170
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000768
Gnomad4 FIN exome
AF:
0.0000209
Gnomad4 NFE exome
AF:
0.000315
Gnomad4 OTH exome
AF:
0.000122
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000669
AC:
102
AN:
152366
Hom.:
0
Cov.:
34
AF XY:
0.000658
AC XY:
49
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00200
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000365
Hom.:
0
Bravo
AF:
0.000740

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022ADAMTS7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
0.22
Dann
Benign
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371317043; hg19: chr15-79056346; API