11-70087884-A-C

Variant names:

• chr11-70087884-A-C
• NM_018043.7:c.241A>C
• ANO1 p.Arg81Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018043.7(ANO1):​c.241A>C​(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R81R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANO1 NM_018043.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.719 with no splicing effect.

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.241A>C	p.Arg81Arg	synonymous	Exon 2 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.364A>C	p.Arg122Arg	synonymous	Exon 3 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.241A>C	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.241A>C	p.Arg81Arg	synonymous	Exon 2 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.364A>C	p.Arg122Arg	synonymous	Exon 3 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.241A>C	p.Arg81Arg	synonymous	Exon 3 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		0.72

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-69933990;