2-241190168-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001370694.2(ANO7):c.105G>A(p.Ser35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,558,282 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0096 (35 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (26 hom.)
• Consequence: ANO7 NM_001370694.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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=-0.86).
• BP6: Variant 2-241190168-G-A is Benign according to our data. Variant chr2-241190168-G-A is described in ClinVar as [Benign]. Clinvar id is 709659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00965 (1469/152262) while in subpopulation AFR AF= 0.0324 (1346/41536). AF 95% confidence interval is 0.031. There are 35 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO7	NM_001370694.2	c.105G>A	p.Ser35=	synonymous_variant	2/25	ENST00000674324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO7	ENST00000674324.2	c.105G>A	p.Ser35=	synonymous_variant	2/25		NM_001370694.2	A2
ANO7	ENST00000274979.12	c.267G>A	p.Ser89=	synonymous_variant	2/25	1		P2
ANO7	ENST00000402530.8	c.105G>A	p.Ser35=	synonymous_variant	2/4	1
ANO7	ENST00000402430.8	c.105G>A	p.Ser35=	synonymous_variant	2/22	5

Frequencies

GnomAD3 genomes AF: 0.00966 AC: 1469 AN: 152144 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00306 AC: 501 AN: 163706 Hom.: 5 AF XY: 0.00246 AC XY: 213 AN XY: 86720

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000260

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000201

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00143 AC: 2017 AN: 1406020 Hom.: 26 Cov.: 31 AF XY: 0.00133 AC XY: 925 AN XY: 694274

Gnomad4 AFR exome AF: 0.0347

Gnomad4 AMR exome AF: 0.00173

Gnomad4 ASJ exome AF: 0.0193

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.000251

Gnomad4 FIN exome AF: 0.0000610

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00334

GnomAD4 genome AF: 0.00965 AC: 1469 AN: 152262 Hom.: 35 Cov.: 33 AF XY: 0.00872 AC XY: 649 AN XY: 74446

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00387 Hom.: 3

Bravo AF: 0.0109

Asia WGS AF: 0.00144 AC: 6 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

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.0
Dann	Benign	0.48

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

Other links and lift over

dbSNP: rs61749471; hg19: chr2-242129583;