chr11-70078649-C-G

Variant names:

• chr11-70078649-C-G
• rs199763025
• NM_018043.7:c.43C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018043.7(ANO1):​c.43C>G​(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO1 NM_018043.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 7 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]

LINC02584 (HGNC:33275): (long intergenic non-protein coding RNA 2584)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20372975).

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.43C>G	p.Arg15Gly	missense	Exon 1 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.166C>G	p.Arg56Gly	missense	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.43C>G	p.Arg15Gly	missense	Exon 2 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.43C>G	p.Arg15Gly	missense	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.166C>G	p.Arg56Gly	missense	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.43C>G	p.Arg15Gly	missense	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149298 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1352618 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 673200

African (AFR) AF: 0.00 AC: 0 AN: 27140

American (AMR) AF: 0.00 AC: 0 AN: 37618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21910

East Asian (EAS) AF: 0.00 AC: 0 AN: 29002

South Asian (SAS) AF: 0.00 AC: 0 AN: 81254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048566

Other (OTH) AF: 0.00 AC: 0 AN: 53464

GnomAD4 genome AF: 0.00000670 AC: 1 AN: 149298 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 72760

African (AFR) AF: 0.00 AC: 0 AN: 41192

American (AMR) AF: 0.00 AC: 0 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 66964

Other (OTH) AF: 0.00 AC: 0 AN: 2048

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.093
Sift	Uncertain	0.020	D
Sift4G	Benign	0.28	T
Polyphen		0.013	B
Vest4		0.21
MutPred		0.38		Loss of sheet (P = 0.0457)
MVP		0.51
MPC		0.58
ClinPred		0.29	T
GERP RS		2.2
PromoterAI		0.048	Neutral
Varity_R		0.14
gMVP		0.40
Mutation Taster		=93/7	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: rs199763025; hg19: chr11-69924755;