rs10834976

Positions:

• chr11-26424644-G-A
• chr11-26424644-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031418.4(ANO3):​c.47-17274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,986 control chromosomes in the GnomAD database, including 49,008 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 0.78 (49008 hom., cov: 31)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

Genes affected

ANO3 (HGNC:14004): (anoctamin 3) The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.47-17274G>A		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.230-17274G>A		intron_variant
ANO3	XM_047427399.1	c.47-17274G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.47-17274G>A		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-2-17274G>A		intron_variant		5
ANO3	ENST00000531646.1	c.47-17274G>A		intron_variant		4
ANO3	ENST00000672621.1	c.230-17274G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118975 AN: 151868 Hom.: 49002 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.783 AC: 119001 AN: 151986 Hom.: 49008 Cov.: 31 AF XY: 0.788 AC XY: 58584 AN XY: 74306

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.823

Alfa AF: 0.872 Hom.: 57968

Bravo AF: 0.768

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.40

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: rs10834976; hg19: chr11-26446191;