rs11029621

Positions:

• chr11-26575451-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+15672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,700 control chromosomes in the GnomAD database, including 18,252 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 0.49 (18252 hom., cov: 32)
• Consequence: ANO3 NM_031418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO3	NM_031418.4	c.1447+15672G>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+15672G>A		intron_variant		1	NM_031418.4	ENSP00000256737	P3
ANO3	ENST00000525139.5	c.1399+15672G>A		intron_variant		5		ENSP00000432576
ANO3	ENST00000531568.1	c.1009+15672G>A		intron_variant		2		ENSP00000432394	A1
ANO3	ENST00000672621.1	c.1630+15672G>A		intron_variant				ENSP00000500506

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74121 AN: 151578 Hom.: 18243 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.489 AC: 74156 AN: 151700 Hom.: 18252 Cov.: 32 AF XY: 0.491 AC XY: 36421 AN XY: 74120

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.476

Alfa AF: 0.498 Hom.: 2327

Bravo AF: 0.473

Asia WGS AF: 0.526 AC: 1774 AN: 3370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.6
DANN	Benign	0.36

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: rs11029621; hg19: chr11-26596998;