rs2509175

chr11-70132532-T-Achr11-70132532-T-Cchr11-70132532-T-G

Variant summary

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

The NM_018043.7(ANO1):c.1258+453T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,118 control chromosomes in the GnomAD database, including 5,982 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 0.26 (5982 hom., cov: 32)
• Consequence: ANO1 NM_018043.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO1	NM_018043.7	c.1258+453T>A		intron_variant		ENST00000355303.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO1	ENST00000355303.10	c.1258+453T>A		intron_variant		1	NM_018043.7	P2
	ENST00000530525.1	n.422+2814T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39905 AN: 152000 Hom.: 5966 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.263 AC: 39962 AN: 152118 Hom.: 5982 Cov.: 32 AF XY: 0.256 AC XY: 19020 AN XY: 74372

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0933

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.275

Alfa AF: 0.245 Hom.: 618

Bravo AF: 0.273

Asia WGS AF: 0.160 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.71

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: rs2509175; hg19: chr11-69978638;