rs2276068

Positions:

• chr11-70161378-C-G

Variant summary

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

The NM_018043.7(ANO1):​c.1780+16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,611,890 control chromosomes in the GnomAD database, including 223,894 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 0.48 (18620 hom., cov: 33)
  • Exomes 𝑓: 0.53 (205274 hom.)
• Consequence: ANO1 NM_018043.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

Genes affected

ANO1 (HGNC:21625): (anoctamin 1) Enables calcium activated cation channel activity; intracellular calcium activated chloride channel activity; and iodide transmembrane transporter activity. Involved in cation transport; inorganic anion transport; and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in apical plasma membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO1	NM_018043.7	c.1780+16C>G		intron_variant		ENST00000355303.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO1	ENST00000355303.10	c.1780+16C>G		intron_variant		1	NM_018043.7	P2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73517 AN: 151974 Hom.: 18619 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.462

GnomAD3 exomes AF: 0.541 AC: 134416 AN: 248316 Hom.: 37175 AF XY: 0.540 AC XY: 72727 AN XY: 134702

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.555

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.701

Gnomad SAS exome AF: 0.517

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.527 AC: 769024 AN: 1459798 Hom.: 205274 Cov.: 45 AF XY: 0.527 AC XY: 382995 AN XY: 726252

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.761

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.484 AC: 73564 AN: 152092 Hom.: 18620 Cov.: 33 AF XY: 0.489 AC XY: 36389 AN XY: 74352

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.456

Alfa AF: 0.513 Hom.: 3782

Bravo AF: 0.467

Asia WGS AF: 0.608 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.30

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: rs2276068; hg19: chr11-70007484; COSMIC: COSV60284967; COSMIC: COSV60284967;