rs873860

Positions:

• chr11-70095680-C-T

Variant summary

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

The NM_018043.7(ANO1):​c.442-7386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,076 control chromosomes in the GnomAD database, including 8,065 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 0.31 (8065 hom., cov: 32)
• Consequence: ANO1 NM_018043.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO1	NM_018043.7	c.442-7386C>T		intron_variant		ENST00000355303.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO1	ENST00000355303.10	c.442-7386C>T		intron_variant		1	NM_018043.7	P2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47754 AN: 151958 Hom.: 8052 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.314 AC: 47790 AN: 152076 Hom.: 8065 Cov.: 32 AF XY: 0.322 AC XY: 23941 AN XY: 74340

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.306

Alfa AF: 0.333 Hom.: 14002

Bravo AF: 0.305

Asia WGS AF: 0.372 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.79

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: rs873860; hg19: chr11-69941786;