11-26331890-C-G

Position:

• chr11-26331890-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_931138.3(LOC105376598):​n.85G>C variant causes a non coding transcript exon 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: LOC105376598 XR_931138.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694

Genes affected

LOC105376598 (HGNC:):

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376598	XR_931138.3	n.85G>C		non_coding_transcript_exon_variant	1/3
ANO3	NM_001313726.2	c.229+22171C>G		intron_variant			NP_001300655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO3	ENST00000525139.5	c.-3+22171C>G		intron_variant		5		ENSP00000432576
ANO3	ENST00000672621.1	c.229+22171C>G		intron_variant				ENSP00000500506

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.000398

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000216

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00228

Gnomad4 OTH exome AF: 0.0186

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

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0311 Hom.: 47

Bravo AF: 0.0595

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.8
DANN	Benign	0.80

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: rs16915482; hg19: chr11-26353437;