chr11-70078697-C-G

Variant names:

• chr11-70078697-C-G
• rs765946675
• NM_018043.7:c.91C>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.91C>G​(p.Leu31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,337,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ANO1 NM_018043.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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]

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=0.12839842).

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.91C>G	p.Leu31Val	missense	Exon 1 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.214C>G	p.Leu72Val	missense	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.91C>G	p.Leu31Val	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.91C>G	p.Leu31Val	missense	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.214C>G	p.Leu72Val	missense	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.91C>G	p.Leu31Val	missense	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 192996 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1337244 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 665672

African (AFR) AF: 0.00 AC: 0 AN: 26572

American (AMR) AF: 0.00 AC: 0 AN: 36102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21300

East Asian (EAS) AF: 0.00 AC: 0 AN: 27892

South Asian (SAS) AF: 0.00 AC: 0 AN: 79966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1039980

Other (OTH) AF: 0.00 AC: 0 AN: 52418

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.084
Sift	Benign	0.49	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.38		Loss of helix (P = 0.0033)
MVP		0.23
MPC		0.42
ClinPred		0.15	T
GERP RS		3.4
PromoterAI		0.17	Neutral
Varity_R		0.097
gMVP		0.24
Mutation Taster		=92/8	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: rs765946675; hg19: chr11-69924803;