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GeneBe

15-78763726-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014272.5(ADAMTS7):c.4713G>T(p.Thr1571=) 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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

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=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-78763726-C-A is Benign according to our data. Variant chr15-78763726-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645614.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=-1.68 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTS7NM_014272.5 linkuse as main transcriptc.4713G>T p.Thr1571= synonymous_variant 22/24 ENST00000388820.5
ADAMTS7XM_047432122.1 linkuse as main transcriptc.4713G>T p.Thr1571= synonymous_variant 22/24
ADAMTS7XM_047432123.1 linkuse as main transcriptc.3954G>T p.Thr1318= synonymous_variant 21/23
ADAMTS7XM_011521166.3 linkuse as main transcriptc.2967G>T p.Thr989= synonymous_variant 11/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTS7ENST00000388820.5 linkuse as main transcriptc.4713G>T p.Thr1571= synonymous_variant 22/241 NM_014272.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00682
AC:
1039
AN:
152256
Hom.:
16
Cov.:
34
show subpopulations
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
GnomAD3 exomes
AF:
0.00610
AC:
1299
AN:
213010
Hom.:
13
AF XY:
0.00590
AC XY:
695
AN XY:
117846
show subpopulations
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 SAS exome
AF:
0.000599
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
show subpopulations
Gnomad4 AFR exome
AF:
0.000803
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00116
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000560
Gnomad4 FIN exome
AF:
0.0307
Gnomad4 NFE exome
AF:
0.00567
Gnomad4 OTH exome
AF:
0.00522
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00682
AC:
1039
AN:
152374
Hom.:
16
Cov.:
34
AF XY:
0.00833
AC XY:
621
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000769
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.0398
Gnomad4 NFE
AF:
0.00807
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00959
Hom.:
3
Bravo
AF:
0.00319

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 TuebingenMar 01, 2023ADAMTS7: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
0.024
Dann
Benign
0.78

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

Publications

LitVar

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

Other links and lift over

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