Variant 2-241188700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000274979.12(ANO7):c.89G>A(p.Arg30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

ANO7
ENST00000274979.12 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.23

Variant links:

Genes affected

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ANO7 links:

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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=0.0059781373).

BP6

Variant 2-241188700-G-A is Benign according to our data. Variant chr2-241188700-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2411607.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO7	NM_001370694.2 linkuse as main transcript	c.-74G>A		5_prime_UTR_variant	1/25	ENST00000674324.2	NP_001357623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO7	ENST00000274979.12 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	1/25	1		ENSP00000274979	P2	Q6IWH7-1
ANO7	ENST00000674324.2 linkuse as main transcript	c.-74G>A		5_prime_UTR_variant	1/25		NM_001370694.2	ENSP00000501393	A2
ANO7	ENST00000402530.8 linkuse as main transcript	c.-74G>A		5_prime_UTR_variant	1/4	1		ENSP00000383985
ANO7	ENST00000402430.8 linkuse as main transcript	c.-74G>A		5_prime_UTR_variant	1/22	5		ENSP00000385418

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000277

AC:

AN:

248846

Hom.:

AF XY:

0.000289

AC XY:

AN XY:

134870

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461306

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000598

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.000669

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Apr 25, 2022

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

0.083

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.028

.;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.058

MVP

0.12

MPC

0.13

ClinPred

0.0038

GERP RS

-4.4

Varity_R

0.017

gMVP

0.18

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.

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