chr12-5595718-C-A

Variant names:

• chr12-5595718-C-A
• rs4140862
• NM_001364791.2:c.2233+3766G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364791.2(ANO2):​c.2233+3766G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,996 control chromosomes in the GnomAD database, including 6,702 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6702 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 1 publications found

Genes affected

ANO2 (HGNC:1183): (anoctamin 2) ANO2 belongs to a family of calcium-activated chloride channels (CaCCs) (reviewed by Hartzell et al., 2009 [PubMed 19015192]).[supplied by OMIM, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364791.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	NM_001364791.2	MANE Select	c.2233+3766G>T		intron	N/A	NP_001351720.1
	ANO2	NM_001278596.3		c.2248+3766G>T		intron	N/A	NP_001265525.1
	ANO2	NM_001278597.3		c.2236+3766G>T		intron	N/A	NP_001265526.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	ENST00000682330.1	MANE Select	c.2233+3766G>T		intron	N/A	ENSP00000507275.1
	ANO2	ENST00000650848.1		c.2248+3766G>T		intron	N/A	ENSP00000498903.1
	ANO2	ENST00000356134.9	TSL:5	c.2236+3766G>T		intron	N/A	ENSP00000348453.5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44579 AN: 151878 Hom.: 6695 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44607 AN: 151996 Hom.: 6702 Cov.: 32 AF XY: 0.290 AC XY: 21533 AN XY: 74316

African (AFR) AF: 0.229 AC: 9497 AN: 41444

American (AMR) AF: 0.318 AC: 4851 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3464

East Asian (EAS) AF: 0.193 AC: 997 AN: 5168

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3048 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22724 AN: 67952

Other (OTH) AF: 0.301 AC: 636 AN: 2110

Alfa AF: 0.286 Hom.: 2452

Bravo AF: 0.295

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.72
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4140862; hg19: chr12-5704884;