2-241190072-G-T

Variant names:

• chr2-241190072-G-T
• rs11695874
• NM_001370694.2:c.9G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001370694.2(ANO7):​c.9G>T​(p.Arg3Arg) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.145
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -21 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 VariationId is 1182026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370694.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO7	NM_001370694.2	MANE Select	c.9G>T	p.Arg3Arg	synonymous	Exon 2 of 25	NP_001357623.1	A0A6I8PRE6
	ANO7	NM_001001666.4		c.9G>T	p.Arg3Arg	synonymous	Exon 2 of 4	NP_001001666.2	A0A6Q8JT31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO7	ENST00000674324.2	MANE Select	c.9G>T	p.Arg3Arg	synonymous	Exon 2 of 25	ENSP00000501393.1	A0A6I8PRE6
	ANO7	ENST00000274979.12	TSL:1	c.171G>T	p.Arg57Arg	synonymous	Exon 2 of 25	ENSP00000274979.8	Q6IWH7-1
	ANO7	ENST00000402530.8	TSL:1	c.9G>T	p.Arg3Arg	synonymous	Exon 2 of 4	ENSP00000383985.4	A0A6Q8JT31

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

GnomAD2 exomes AF: 0.215 AC: 40907 AN: 189942 AF XY: 0.216

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 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

African (AFR) AF: 0.120 AC: 3923 AN: 32804

American (AMR) AF: 0.174 AC: 6732 AN: 38756

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5368 AN: 25384

East Asian (EAS) AF: 0.0166 AC: 627 AN: 37712

South Asian (SAS) AF: 0.169 AC: 13668 AN: 80890

European-Finnish (FIN) AF: 0.293 AC: 14697 AN: 50090

Middle Eastern (MID) AF: 0.229 AC: 1284 AN: 5604

European-Non Finnish (NFE) AF: 0.288 AC: 314202 AN: 1092214

Other (OTH) AF: 0.241 AC: 14184 AN: 58926

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

African (AFR) AF: 0.124 AC: 5158 AN: 41534

American (AMR) AF: 0.211 AC: 3231 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3472

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5184

South Asian (SAS) AF: 0.160 AC: 771 AN: 4826

European-Finnish (FIN) AF: 0.291 AC: 3080 AN: 10586

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19503 AN: 67924

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.256 Hom.: 2694

Bravo AF: 0.207

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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