chr2-241188700-G-A

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

19

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]

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=0.0059781373).
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
ANO7NM_001370694.2 linkuse as main transcriptc.-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
ANO7ENST00000274979.12 linkuse as main transcriptc.89G>A p.Arg30Gln missense_variant 1/251 ENSP00000274979 P2Q6IWH7-1
ANO7ENST00000674324.2 linkuse as main transcriptc.-74G>A 5_prime_UTR_variant 1/25 NM_001370694.2 ENSP00000501393 A2
ANO7ENST00000402530.8 linkuse as main transcriptc.-74G>A 5_prime_UTR_variant 1/41 ENSP00000383985
ANO7ENST00000402430.8 linkuse as main transcriptc.-74G>A 5_prime_UTR_variant 1/225 ENSP00000385418

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152144
Hom.:
0
Cov.:
32
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:
69
AN:
248846
Hom.:
1
AF XY:
0.000289
AC XY:
39
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.:
1
Cov.:
31
AF XY:
0.000114
AC XY:
83
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:
91
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.000833
AC XY:
62
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.:
0
Bravo
AF:
0.000669
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
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 submitterclinical testingAmbry GeneticsApr 25, 2022This 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
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
12
DANN
Benign
0.82
DEOGEN2
Benign
0.028
.;T;.
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.48
T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.0060
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.32
T
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
T
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.

Other links and lift over

dbSNP: rs150946357; hg19: chr2-242128115; COSMIC: COSV51478746; API