11-70087886-G-A

Variant names:

• chr11-70087886-G-A
• rs369009893
• NM_018043.7:c.243G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018043.7(ANO1):​c.243G>A​(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,612,160 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (5 hom.)
• Consequence: ANO1 NM_018043.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.102
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-70087886-G-A is Benign according to our data. Variant chr11-70087886-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 774696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.102 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR,AD gene

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.243G>A	p.Arg81Arg	synonymous	Exon 2 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.366G>A	p.Arg122Arg	synonymous	Exon 3 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.243G>A	p.Arg81Arg	synonymous	Exon 3 of 26	NP_001365022.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO1	ENST00000355303.10	TSL:1 MANE Select	c.243G>A	p.Arg81Arg	synonymous	Exon 2 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.366G>A	p.Arg122Arg	synonymous	Exon 3 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.243G>A	p.Arg81Arg	synonymous	Exon 3 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 202 AN: 152116 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00143 AC: 347 AN: 243144 AF XY: 0.00152

Gnomad AFR exome AF: 0.000531

Gnomad AMR exome AF: 0.000497

Gnomad ASJ exome AF: 0.00403

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00211

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.00202

GnomAD4 exome AF: 0.00211 AC: 3080 AN: 1459926 Hom.: 5 Cov.: 31 AF XY: 0.00206 AC XY: 1494 AN XY: 726152

African (AFR) AF: 0.000269 AC: 9 AN: 33474

American (AMR) AF: 0.000605 AC: 27 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00418 AC: 109 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00102 AC: 88 AN: 85936

European-Finnish (FIN) AF: 0.00205 AC: 108 AN: 52596

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00235 AC: 2613 AN: 1111484

Other (OTH) AF: 0.00201 AC: 121 AN: 60310

GnomAD4 genome AF: 0.00133 AC: 202 AN: 152234 Hom.: 1 Cov.: 31 AF XY: 0.00129 AC XY: 96 AN XY: 74430

African (AFR) AF: 0.000361 AC: 15 AN: 41548

American (AMR) AF: 0.000784 AC: 12 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00177 Hom.: 1

Bravo AF: 0.00120

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.80
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

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: rs369009893; hg19: chr11-69933992;