rs16915482

Variant names:

• chr11-26331890-C-G
• rs16915482
• NM_001313726.2:c.229+22171C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001313726.2(ANO3):​c.229+22171C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 224,388 control chromosomes in the GnomAD database, including 714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (669 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (45 hom.)
• Consequence: ANO3 NM_001313726.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694
• Publications: 0 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-AS1 (HGNC:54190): (ANO3 antisense RNA 1)

LOC105376598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-26331890-C-G is Benign according to our data. Variant chr11-26331890-C-G is described in ClinVar as Benign. ClinVar VariationId is 1249029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313726.2. 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_001313726.2		c.229+22171C>G		intron	N/A	NP_001300655.1	A0A5F9ZHL6
	ANO3	NM_031418.4	MANE Select	c.-386C>G		upstream_gene	N/A	NP_113606.2	Q9BYT9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO3	ENST00000672621.1		c.229+22171C>G		intron	N/A	ENSP00000500506.1	A0A5F9ZHL6
	ANO3	ENST00000525139.5	TSL:5	c.-3+22171C>G		intron	N/A	ENSP00000432576.1	E9PQ79
	ANO3-AS1	ENST00000743407.1		n.117G>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8023 AN: 152174 Hom.: 666 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.00902 AC: 650 AN: 72096 Hom.: 45 Cov.: 2 AF XY: 0.00814 AC XY: 301 AN XY: 36960

African (AFR) AF: 0.167 AC: 390 AN: 2336

American (AMR) AF: 0.0180 AC: 55 AN: 3058

Ashkenazi Jewish (ASJ) AF: 0.000398 AC: 1 AN: 2514

East Asian (EAS) AF: 0.00 AC: 0 AN: 4152

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3798

Middle Eastern (MID) AF: 0.0292 AC: 10 AN: 342

European-Non Finnish (NFE) AF: 0.00228 AC: 106 AN: 46590

Other (OTH) AF: 0.0186 AC: 87 AN: 4680

GnomAD4 genome AF: 0.0528 AC: 8042 AN: 152292 Hom.: 669 Cov.: 32 AF XY: 0.0512 AC XY: 3814 AN XY: 74480

African (AFR) AF: 0.178 AC: 7379 AN: 41536

American (AMR) AF: 0.0262 AC: 401 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00198 AC: 135 AN: 68032

Other (OTH) AF: 0.0521 AC: 110 AN: 2110

Alfa AF: 0.0311 Hom.: 47

Bravo AF: 0.0595

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.8
DANN	Benign	0.80
PhyloP100		-0.69
PromoterAI		0.0040	Neutral
Mutation Taster		=300/0	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: rs16915482; hg19: chr11-26353437;