11-70132532-T-A

Variant names:

• chr11-70132532-T-A
• rs2509175
• NM_018043.7:c.1258+453T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ANO1 Gene-Disease associations (from GenCC):

• moyamoya disease 7

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intestinal dysmotility syndrome

  Inheritance: AR Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000255143 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018043.7. 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
	ANO1	NM_018043.7	MANE Select	c.1258+453T>A		intron	N/A	NP_060513.5
	ANO1	NM_001378092.1		c.1447+453T>A		intron	N/A	NP_001365021.1
	ANO1	NM_001378093.1		c.1258+453T>A		intron	N/A	NP_001365022.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO1	ENST00000355303.10	TSL:1 MANE Select	c.1258+453T>A		intron	N/A	ENSP00000347454.5
	ANO1	ENST00000531349.6	TSL:1	c.1447+453T>A		intron	N/A	ENSP00000432843.2
	ANO1	ENST00000930664.1		c.1324+453T>A		intron	N/A	ENSP00000600723.1

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

African (AFR) AF: 0.416 AC: 17249 AN: 41488

American (AMR) AF: 0.180 AC: 2750 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3470

East Asian (EAS) AF: 0.0933 AC: 482 AN: 5168

South Asian (SAS) AF: 0.164 AC: 790 AN: 4822

European-Finnish (FIN) AF: 0.150 AC: 1594 AN: 10592

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15042 AN: 67974

Other (OTH) AF: 0.275 AC: 580 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.033
Mutation Taster		=100/0	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: rs2509175; hg19: chr11-69978638;