rs12579637

chr12-100879405-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ANO4	NM_001286615.2	c.-140-22241G>A		intron_variant		ENST00000392977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO4	ENST00000392977.8	c.-140-22241G>A		intron_variant		2	NM_001286615.2

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

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.198

Alfa AF: 0.216 Hom.: 2640

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

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: rs12579637; hg19: chr12-101273183;