2-241190072-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001370694.2(ANO7):c.9G>T(p.Arg3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,574,504 control chromosomes in the GnomAD database, including 56,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4137 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52103 hom.)
• Consequence: ANO7 NM_001370694.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.145

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-241190072-G-T is Benign according to our data. Variant chr2-241190072-G-T is described in ClinVar as [Benign]. Clinvar id is 1182026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.145 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO7	NM_001370694.2	c.9G>T	p.Arg3=	synonymous_variant	2/25	ENST00000674324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO7	ENST00000674324.2	c.9G>T	p.Arg3=	synonymous_variant	2/25		NM_001370694.2	A2
ANO7	ENST00000274979.12	c.171G>T	p.Arg57=	synonymous_variant	2/25	1		P2
ANO7	ENST00000402530.8	c.9G>T	p.Arg3=	synonymous_variant	2/4	1
ANO7	ENST00000402430.8	c.9G>T	p.Arg3=	synonymous_variant	2/22	5

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33339 AN: 152006 Hom.: 4135 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.215 AC: 40907 AN: 189942 Hom.: 5062 AF XY: 0.216 AC XY: 21929 AN XY: 101578

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0215

Gnomad SAS exome AF: 0.167

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.263 AC: 374685 AN: 1422380 Hom.: 52103 Cov.: 33 AF XY: 0.260 AC XY: 183164 AN XY: 703762

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.219 AC: 33347 AN: 152124 Hom.: 4137 Cov.: 32 AF XY: 0.217 AC XY: 16171 AN XY: 74358

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.226

Alfa AF: 0.256 Hom.: 2694

Bravo AF: 0.207

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs11695874; hg19: chr2-242129487; COSMIC: COSV51480081;