8-24500828-G-A

Position:

chr8-24500828-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003817.4(ADAM7):c.2041G>A(p.Val681Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ADAM7
NM_003817.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.216

Variant links:

Genes affected

ADAM7 (HGNC:214): (ADAM metallopeptidase domain 7) This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma. [provided by RefSeq, Oct 2011]

ADAM7 links:

ADAM7-AS2 (HGNC:56153): (ADAM7 antisense RNA 2)

ADAM7-AS2 links:

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ADAM7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03124851).

BP6

Variant 8-24500828-G-A is Benign according to our data. Variant chr8-24500828-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3145924.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAM7	NM_003817.4 linkuse as main transcript	c.2041G>A	p.Val681Ile	missense_variant	19/22	ENST00000175238.10	NP_003808.2
ADAM7-AS1	NR_125808.1 linkuse as main transcript	n.79+47712C>T		intron_variant, non_coding_transcript_variant
ADAM7-AS2	NR_125809.1 linkuse as main transcript	n.447-8668C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10 linkuse as main transcript	c.2041G>A	p.Val681Ile	missense_variant	19/22	1	NM_003817.4	ENSP00000175238	P2	Q9H2U9-1
ADAM7-AS2	ENST00000519364.5 linkuse as main transcript	n.407-8668C>T		intron_variant, non_coding_transcript_variant		5
ADAM7-AS1	ENST00000519689.1 linkuse as main transcript	n.185-112837C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251062

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.000123

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

AF:

0.00000342

AC:

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000957

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.035

DANN

Benign

0.70

DEOGEN2

Benign

0.0015

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.016

Sift

Benign

0.61

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.15

MutPred

0.30

Gain of catalytic residue at L686 (P = 0.103);Gain of catalytic residue at L686 (P = 0.103);.;

MVP

0.23

MPC

0.041

ClinPred

0.017

GERP RS

-8.6

Varity_R

0.026

gMVP

0.20

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over