rs1461361

chr11-26420336-C-T

Variant summary

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

The NM_031418.4(ANO3):c.47-21582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,002 control chromosomes in the GnomAD database, including 1,271 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 0.091 (1271 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO3	NM_031418.4	c.47-21582C>T		intron_variant		ENST00000256737.8
ANO3	NM_001313726.2	c.230-21582C>T		intron_variant
ANO3	XM_047427399.1	c.47-21582C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO3	ENST00000256737.8	c.47-21582C>T		intron_variant		1	NM_031418.4	P3
ANO3	ENST00000525139.5	c.-2-21582C>T		intron_variant		5
ANO3	ENST00000531646.1	c.47-21582C>T		intron_variant		4
ANO3	ENST00000672621.1	c.230-21582C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13758 AN: 151882 Hom.: 1267 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0628

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

GnomAD4 genome AF: 0.0907 AC: 13792 AN: 152002 Hom.: 1271 Cov.: 32 AF XY: 0.0884 AC XY: 6572 AN XY: 74312

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0454 Hom.: 178

Bravo AF: 0.0989

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.0
Dann	Benign	0.53

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: rs1461361; hg19: chr11-26441883;