Variant 11-70103072-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018043.7(ANO1):c.448A>G(p.Ile150Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000869 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ANO1
NM_018043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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:

ANO1 (HGNC:):

ANO1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08603454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO1	NM_018043.7 linkuse as main transcript	c.448A>G	p.Ile150Val	missense_variant	3/26	ENST00000355303.10	NP_060513.5	Q5XXA6-1Q9NW72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO1	ENST00000355303.10 linkuse as main transcript	c.448A>G	p.Ile150Val	missense_variant	3/26	1	NM_018043.7	ENSP00000347454.5		Q5XXA6-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243208

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132066

show subpopulations

Gnomad AFR exome

AF:

0.000137

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000617

AC:

AN:

1458292

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725048

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000677

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000907

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.448A>G (p.I150V) alteration is located in exon 3 (coding exon 3) of the ANO1 gene. This alteration results from a A to G substitution at nucleotide position 448, causing the isoleucine (I) at amino acid position 150 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.098

T;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.088

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.28

MutPred

0.28

Gain of methylation at K149 (P = 0.0759);.;.;

MVP

0.40

MPC

0.38

ClinPred

0.063

GERP RS

5.1

Varity_R

0.037

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over