Genetic Variant ANO1:c.1780+16C>G (chr11-70161378-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018043.7(ANO1):c.1780+16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,611,890 control chromosomes in the GnomAD database, including 223,894 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18620 hom., cov: 33)

Exomes 𝑓: 0.53 ( 205274 hom. )

Consequence

ANO1
NM_018043.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.238

Publications

7 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 Gene-Disease associations (from GenCC):

moyamoya disease 7
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intestinal dysmotility syndrome
Inheritance: AR Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ANO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO1	NM_018043.7 link	c.1780+16C>G		intron_variant	Intron 17 of 25	ENST00000355303.10	NP_060513.5	Q5XXA6-1Q9NW72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO1	ENST00000355303.10 link	c.1780+16C>G		intron_variant	Intron 17 of 25	1	NM_018043.7	ENSP00000347454.5		Q5XXA6-1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73517

AN:

151974

Hom.:

18619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.462

GnomAD2 exomes

AF:

0.541

AC:

134416

AN:

248316

AF XY:

0.540

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.701

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.527

AC:

769024

AN:

1459798

Hom.:

205274

Cov.:

AF XY:

0.527

AC XY:

382995

AN XY:

726252

show subpopulations

African (AFR)

AF:

0.330

AC:

11025

AN:

33446

American (AMR)

AF:

0.549

AC:

24532

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

13681

AN:

26118

East Asian (EAS)

AF:

0.761

AC:

30195

AN:

39688

South Asian (SAS)

AF:

0.515

AC:

44359

AN:

86202

European-Finnish (FIN)

AF:

0.633

AC:

33669

AN:

53192

Middle Eastern (MID)

AF:

0.444

AC:

2556

AN:

5762

European-Non Finnish (NFE)

AF:

0.520

AC:

577829

AN:

1110364

Other (OTH)

AF:

0.517

AC:

31178

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18527

37053

55580

74106

92633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16576

33152

49728

66304

82880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.484

AC:

73564

AN:

152092

Hom.:

18620

Cov.:

AF XY:

0.489

AC XY:

36389

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.340

AC:

14114

AN:

41486

American (AMR)

AF:

0.486

AC:

7432

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1803

AN:

3470

East Asian (EAS)

AF:

0.716

AC:

3704

AN:

5170

South Asian (SAS)

AF:

0.530

AC:

2555

AN:

4818

European-Finnish (FIN)

AF:

0.634

AC:

6716

AN:

10600

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.525

AC:

35705

AN:

67948

Other (OTH)

AF:

0.456

AC:

964

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1935

3870

5806

7741

9676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.513

Hom.:

3782

Bravo

AF:

0.467

Asia WGS

AF:

0.608

AC:

2113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.30

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over