rs1461361

Variant names:

• chr11-26420336-C-T
• rs1461361
• NM_031418.4:c.47-21582C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ANO3 Gene-Disease associations (from GenCC):

• dystonia 24

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANO3	NM_031418.4	c.47-21582C>T		intron_variant	Intron 1 of 26	ENST00000256737.8	NP_113606.2
ANO3	NM_001313726.2	c.230-21582C>T		intron_variant	Intron 2 of 27		NP_001300655.1
ANO3	XM_047427399.1	c.47-21582C>T		intron_variant	Intron 1 of 25		XP_047283355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8	c.47-21582C>T		intron_variant	Intron 1 of 26	1	NM_031418.4	ENSP00000256737.3
ANO3	ENST00000672621.1	c.230-21582C>T		intron_variant	Intron 2 of 27			ENSP00000500506.1
ANO3	ENST00000525139.5	c.-2-21582C>T		intron_variant	Intron 1 of 26	5		ENSP00000432576.1
ANO3	ENST00000531646.1	c.47-21582C>T		intron_variant	Intron 1 of 4	4		ENSP00000435275.1

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

African (AFR) AF: 0.243 AC: 10074 AN: 41452

American (AMR) AF: 0.0423 AC: 645 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3468

East Asian (EAS) AF: 0.107 AC: 549 AN: 5144

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4818

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1870 AN: 67964

Other (OTH) AF: 0.0640 AC: 135 AN: 2108

Alfa AF: 0.0460 Hom.: 206

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
PhyloP100		-0.21
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: rs1461361; hg19: chr11-26441883;