Variant 11-70116470-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 ENST00000355303.10(ANO1):c.868G>A(p.Gly290Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,599,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ANO1
ENST00000355303.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

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:

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=0.22879684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO1	NM_018043.7 linkuse as main transcript	c.868G>A	p.Gly290Ser	missense_variant	8/26	ENST00000355303.10	NP_060513.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO1	ENST00000355303.10 linkuse as main transcript	c.868G>A	p.Gly290Ser	missense_variant	8/26	1	NM_018043.7	ENSP00000347454	P2	Q5XXA6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000445

AC:

AN:

224706

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121666

show subpopulations

Gnomad AFR exome

AF:

0.0000749

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1447200

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

718280

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000719

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000253

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

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

May 13, 2022

The c.868G>A (p.G290S) alteration is located in exon 8 (coding exon 8) of the ANO1 gene. This alteration results from a G to A substitution at nucleotide position 868, causing the glycine (G) at amino acid position 290 to be replaced by a serine (S). 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

0.091

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Benign

0.26

DEOGEN2

Benign

0.078

T;.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.66

T;T;T;T

Sift4G

Benign

0.91

T;T;T;T

Polyphen

0.18

B;B;.;B

Vest4

0.50

MutPred

0.28

Gain of disorder (P = 0.1015);.;.;.;

MVP

0.55

MPC

0.60

ClinPred

0.12

GERP RS

4.4

Varity_R

0.11

gMVP

0.58

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