rs293974

Positions:

• chr11-26568579-G-A

Variant summary

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

The NM_031418.4(ANO3):​c.1447+8800G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,524 control chromosomes in the GnomAD database, including 4,573 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 0.24 (4573 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

Genes affected

MUC15 (HGNC:14956): (mucin 15, cell surface associated) Predicted to be located in Golgi lumen and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC15	NM_001135091.2	c.-45-1440C>T		intron_variant		ENST00000529533.6	NP_001128563.1
ANO3	NM_031418.4	c.1447+8800G>A		intron_variant		ENST00000256737.8	NP_113606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000256737.8	c.1447+8800G>A		intron_variant		1	NM_031418.4	ENSP00000256737	P3
MUC15	ENST00000529533.6	c.-45-1440C>T		intron_variant		1	NM_001135091.2	ENSP00000431983

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36486 AN: 151406 Hom.: 4552 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.241 AC: 36546 AN: 151524 Hom.: 4573 Cov.: 32 AF XY: 0.240 AC XY: 17765 AN XY: 74030

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.257

Alfa AF: 0.265 Hom.: 8371

Bravo AF: 0.232

Asia WGS AF: 0.353 AC: 1225 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.17

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: rs293974; hg19: chr11-26590126;