Genetic Variant NM_018043.7:c.82A>G (chr11-70078688-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018043.7(ANO1):c.82A>G(p.Ile28Val) variant causes a missense 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. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANO1
NM_018043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.330

Publications

0 publications found

Variant links:

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 links:

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

LINC02584 links:

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ACMG classification

Classification was made for transcript

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=0.09207934).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO1	NM_018043.7	MANE Select	c.82A>G	p.Ile28Val	missense	Exon 1 of 26	NP_060513.5
ANO1	NM_001378092.1		c.205A>G	p.Ile69Val	missense	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
ANO1	NM_001378093.1		c.82A>G	p.Ile28Val	missense	Exon 2 of 26	NP_001365022.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANO1	ENST00000355303.10	TSL:1 MANE Select	c.82A>G	p.Ile28Val	missense	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
ANO1	ENST00000531349.6	TSL:1	c.205A>G	p.Ile69Val	missense	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
ANO1	ENST00000930664.1		c.82A>G	p.Ile28Val	missense	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1339390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666854

African (AFR)

AF:

0.00

AC:

AN:

26660

American (AMR)

AF:

0.00

AC:

AN:

36328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21380

East Asian (EAS)

AF:

0.00

AC:

AN:

28062

South Asian (SAS)

AF:

0.00

AC:

AN:

80302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1041028

Other (OTH)

AF:

0.00

AC:

AN:

52578

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.11

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.33

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.010

REVEL

Benign

0.10

Sift

Benign

0.91

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.047

MutPred

0.24

Loss of catalytic residue at I28 (P = 0.1122)

MVP

0.23

MPC

0.34

ClinPred

0.027

GERP RS

-6.8

PromoterAI

-0.13

Neutral

(source)

Varity_R

0.026

gMVP

0.26

Mutation Taster

=92/8

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over