rs11110561

Positions:

• chr12-100858549-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.-140-43097A>C		intron_variant		ENST00000392977.8	NP_001273544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000392977.8	c.-140-43097A>C		intron_variant		2	NM_001286615.2	ENSP00000376703
	ENST00000552332.1	n.198+516T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.296

Alfa AF: 0.333 Hom.: 1738

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

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: rs11110561; hg19: chr12-101252327;