rs1531395

Variant names:

• chr11-26332014-T-A
• rs1531395
• NM_001313726.2:c.229+22295T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-26332014-T-A
• chr11-26332014-T-C
• chr11-26332014-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001313726.2(ANO3):​c.229+22295T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,027,388 control chromosomes in the GnomAD database, including 2 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 0.0015 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: ANO3 NM_001313726.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

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]

LOC105376598 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00148 (225/152326) while in subpopulation AFR AF= 0.00467 (194/41580). AF 95% confidence interval is 0.00413. There are 0 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 225 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO3	NM_001313726.2	c.229+22295T>A		intron_variant	Intron 2 of 27		NP_001300655.1
LOC105376598	XR_931138.3	n.-40A>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000672621.1	c.229+22295T>A		intron_variant	Intron 2 of 27			ENSP00000500506.1
ANO3	ENST00000525139.5	c.-3+22295T>A		intron_variant	Intron 1 of 26	5		ENSP00000432576.1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152208 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000278 AC: 243 AN: 875062 Hom.: 2 Cov.: 11 AF XY: 0.000257 AC XY: 112 AN XY: 436568

Gnomad4 AFR exome AF: 0.00457

Gnomad4 AMR exome AF: 0.000654

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000162

Gnomad4 OTH exome AF: 0.000662

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152326 Hom.: 0 Cov.: 34 AF XY: 0.00140 AC XY: 104 AN XY: 74476

Gnomad4 AFR AF: 0.00467

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000150 Hom.: 3321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.93

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: rs1531395; hg19: chr11-26353561;