rs293974

Variant names:

• chr11-26568579-G-A
• rs293974
• NM_031418.4:c.1447+8800G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	NM_031418.4	MANE Select	c.1447+8800G>A		intron	N/A	NP_113606.2	Q9BYT9-1
	MUC15	NM_001135091.2	MANE Select	c.-45-1440C>T		intron	N/A	NP_001128563.1	A0A0A0MT67
	ANO3	NM_001313726.2		c.1630+8800G>A		intron	N/A	NP_001300655.1	A0A5F9ZHL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000256737.8	TSL:1 MANE Select	c.1447+8800G>A		intron	N/A	ENSP00000256737.3	Q9BYT9-1
	MUC15	ENST00000529533.6	TSL:1 MANE Select	c.-45-1440C>T		intron	N/A	ENSP00000431983.1	A0A0A0MT67
	MUC15	ENST00000527569.1	TSL:1	c.-45-1440C>T		intron	N/A	ENSP00000431945.1	A0A0A0MTD6

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

African (AFR) AF: 0.199 AC: 8221 AN: 41330

American (AMR) AF: 0.194 AC: 2941 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1061 AN: 3460

East Asian (EAS) AF: 0.284 AC: 1459 AN: 5136

South Asian (SAS) AF: 0.402 AC: 1936 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2106 AN: 10478

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17927 AN: 67852

Other (OTH) AF: 0.257 AC: 540 AN: 2100

Alfa AF: 0.258 Hom.: 18158

Bravo AF: 0.232

Asia WGS AF: 0.353 AC: 1225 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.17
PhyloP100		-0.088
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: rs293974; hg19: chr11-26590126;