Variant 11-70088079-G-A 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.436G>A(p.Glu146Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000385 in 1,175,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

ANO1
NM_018043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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:

Genome browser will be placed here

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=0.07516047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO1	NM_018043.7 linkuse as main transcript	c.436G>A	p.Glu146Lys	missense_variant	2/26	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.436G>A	p.Glu146Lys	missense_variant	2/26	1	NM_018043.7	ENSP00000347454.5		Q5XXA6-1

Frequencies

GnomAD3 genomes

AF:

0.000168

AC:

AN:

137038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000246

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000251

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000528

GnomAD3 exomes

AF:

0.000173

AC:

AN:

46308

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

22730

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000190

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000413

AC:

429

AN:

1038506

Hom.:

Cov.:

AF XY:

0.000408

AC XY:

202

AN XY:

495436

show subpopulations

Gnomad4 AFR exome

AF:

0.000198

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000271

Gnomad4 SAS exome

AF:

0.0000215

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000445

Gnomad4 OTH exome

AF:

0.000611

GnomAD4 genome

AF:

0.000175

AC:

AN:

137140

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

65798

show subpopulations

Gnomad4 AFR

AF:

0.0000801

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000246

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000251

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000523

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.000143

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

Oct 03, 2022

The c.436G>A (p.E146K) alteration is located in exon 2 (coding exon 2) of the ANO1 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the glutamic acid (E) at amino acid position 146 to be replaced by a lysine (K). 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

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;.

Eigen

Benign

0.046

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;T;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.8

M;.;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.57

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.60

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.0010

B;.;D;.

Vest4

0.47

MVP

0.60

MPC

0.53

ClinPred

0.20

GERP RS

3.4

Varity_R

0.16

gMVP

0.47

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