chr11-70095680-C-T

Variant names:

• chr11-70095680-C-T
• rs873860
• NM_018043.7:c.442-7386C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378092.1(ANO1):​c.565-7386C>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_001378092.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 5 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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378092.1. 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.442-7386C>T		intron	N/A	NP_060513.5
	ANO1	NM_001378092.1		c.565-7386C>T		intron	N/A	NP_001365021.1
	ANO1	NM_001378093.1		c.442-7386C>T		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.442-7386C>T		intron	N/A	ENSP00000347454.5
	ANO1	ENST00000531349.6	TSL:1	c.565-7386C>T		intron	N/A	ENSP00000432843.2
	ANO1	ENST00000930664.1		c.442-7386C>T		intron	N/A	ENSP00000600723.1

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

African (AFR) AF: 0.211 AC: 8765 AN: 41498

American (AMR) AF: 0.420 AC: 6420 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1406 AN: 5150

South Asian (SAS) AF: 0.377 AC: 1821 AN: 4826

European-Finnish (FIN) AF: 0.404 AC: 4268 AN: 10564

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23097 AN: 67974

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.328 Hom.: 33032

Bravo AF: 0.305

Asia WGS AF: 0.372 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.79
PhyloP100		-3.2
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: rs873860; hg19: chr11-69941786;