rs12579637

Variant names:

• chr12-100879405-G-A
• rs12579637
• NM_001286615.2:c.-140-22241G>A

Variant summary

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

The NM_001286615.2(ANO4):​c.-140-22241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,074 control chromosomes in the GnomAD database, including 2,897 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 0.18 (2897 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 4 publications found

Genes affected

ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANO4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.-140-22241G>A		intron_variant	Intron 1 of 27	ENST00000392977.8	NP_001273544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000392977.8	c.-140-22241G>A		intron_variant	Intron 1 of 27	2	NM_001286615.2	ENSP00000376703.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27462 AN: 151956 Hom.: 2894 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.181 AC: 27474 AN: 152074 Hom.: 2897 Cov.: 32 AF XY: 0.180 AC XY: 13375 AN XY: 74342

African (AFR) AF: 0.0731 AC: 3032 AN: 41504

American (AMR) AF: 0.276 AC: 4208 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3468

East Asian (EAS) AF: 0.0849 AC: 440 AN: 5182

South Asian (SAS) AF: 0.172 AC: 829 AN: 4816

European-Finnish (FIN) AF: 0.180 AC: 1901 AN: 10568

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15868 AN: 67966

Other (OTH) AF: 0.198 AC: 418 AN: 2116

Alfa AF: 0.202 Hom.: 3719

Bravo AF: 0.181

Asia WGS AF: 0.133 AC: 460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		0.27
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: rs12579637; hg19: chr12-101273183;