rs11110561

Variant names:

• chr12-100858549-A-C
• rs11110561
• NM_001286615.2:c.-140-43097A>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.-140-43097A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,900 control chromosomes in the GnomAD database, including 6,957 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 (6957 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 1 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

ENSG00000257325 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.-140-43097A>C		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.-140-43097A>C		intron_variant	Intron 1 of 27	2	NM_001286615.2	ENSP00000376703.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44596 AN: 151782 Hom.: 6952 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.294 AC: 44627 AN: 151900 Hom.: 6957 Cov.: 32 AF XY: 0.291 AC XY: 21585 AN XY: 74246

African (AFR) AF: 0.205 AC: 8492 AN: 41440

American (AMR) AF: 0.355 AC: 5404 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3470

East Asian (EAS) AF: 0.151 AC: 780 AN: 5164

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4806

European-Finnish (FIN) AF: 0.283 AC: 2981 AN: 10550

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23933 AN: 67914

Other (OTH) AF: 0.296 AC: 626 AN: 2112

Alfa AF: 0.331 Hom.: 2927

Bravo AF: 0.294

Asia WGS AF: 0.214 AC: 743 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		0.020
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: rs11110561; hg19: chr12-101252327; COSMIC: COSV108156972;