rs12820468

Variant names:

• chr12-101015996-T-C
• rs12820468
• NM_001286615.2:c.735-4038T>C

Variant summary

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

The NM_001286615.2(ANO4):​c.735-4038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,036 control chromosomes in the GnomAD database, including 7,568 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 0.30 (7568 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 3 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

ENSG00000305319 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286615.2. 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
	ANO4	NM_001286615.2	MANE Select	c.735-4038T>C		intron	N/A	NP_001273544.1
	ANO4	NM_001286616.1		c.735-4038T>C		intron	N/A	NP_001273545.1
	ANO4	NM_178826.4		c.630-4038T>C		intron	N/A	NP_849148.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	ENST00000392977.8	TSL:2 MANE Select	c.735-4038T>C		intron	N/A	ENSP00000376703.3
	ANO4	ENST00000644049.1		c.1233-4038T>C		intron	N/A	ENSP00000494481.1
	ANO4	ENST00000392979.7	TSL:2	c.630-4038T>C		intron	N/A	ENSP00000376705.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45973 AN: 151918 Hom.: 7565 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.302 AC: 45985 AN: 152036 Hom.: 7568 Cov.: 32 AF XY: 0.299 AC XY: 22187 AN XY: 74318

African (AFR) AF: 0.185 AC: 7679 AN: 41494

American (AMR) AF: 0.237 AC: 3618 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1152 AN: 5170

South Asian (SAS) AF: 0.289 AC: 1391 AN: 4814

European-Finnish (FIN) AF: 0.343 AC: 3624 AN: 10554

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25690 AN: 67950

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.315 Hom.: 1632

Bravo AF: 0.291

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		-0.28
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: rs12820468; hg19: chr12-101409774;