Genetic Variant ANO9:c.1787-177G>A (chr11-419906-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012302.3(ANO9):c.1787-177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,427,516 control chromosomes in the GnomAD database, including 470,779 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 0.81 ( 49244 hom., cov: 32)

Exomes 𝑓: 0.81 ( 421535 hom. )

Consequence

ANO9
NM_001012302.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

11 publications found

Variant links:

Genes affected

ANO9 (HGNC:20679): (anoctamin 9) The protein encoded by this gene is a member of the TMEM16 (anoctamin) family of proteins, some of which form integral membrane calcium-activated chloride channels. The function of the encoded protein has yet to be elucidated, although it may have channel-forming abilities and also may have phospholipid scramblase activity. This gene has been observed to be upregulated in stage II and III colorectal cancers. [provided by RefSeq, Dec 2016]

ANO9 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO9	NM_001012302.3 link	c.1787-177G>A		intron_variant	Intron 19 of 22	ENST00000332826.7	NP_001012302.2	A1A5B4-1
ANO9	NM_001347882.2 link	c.1355-177G>A		intron_variant	Intron 18 of 21		NP_001334811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO9	ENST00000332826.7 link	c.1787-177G>A		intron_variant	Intron 19 of 22	1	NM_001012302.3	ENSP00000332788.6		A1A5B4-1

Frequencies

GnomAD3 genomes

AF:

0.812

AC:

122008

AN:

150242

Hom.:

49214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.860

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.853

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.962

Gnomad FIN

AF:

0.806

Gnomad MID

AF:

0.901

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.822

GnomAD4 exome

AF:

0.811

AC:

1036365

AN:

1277164

Hom.:

421535

Cov.:

AF XY:

0.815

AC XY:

504851

AN XY:

619204

show subpopulations

African (AFR)

AF:

0.788

AC:

21734

AN:

27592

American (AMR)

AF:

0.767

AC:

15156

AN:

19756

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

15740

AN:

18608

East Asian (EAS)

AF:

0.999

AC:

34706

AN:

34742

South Asian (SAS)

AF:

0.958

AC:

59927

AN:

62532

European-Finnish (FIN)

AF:

0.792

AC:

23441

AN:

29610

Middle Eastern (MID)

AF:

0.908

AC:

3214

AN:

3540

European-Non Finnish (NFE)

AF:

0.796

AC:

817977

AN:

1027822

Other (OTH)

AF:

0.840

AC:

44470

AN:

52962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

11769

23538

35308

47077

58846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20230

40460

60690

80920

101150

<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:

0.812

AC:

122088

AN:

150352

Hom.:

49244

Cov.:

AF XY:

0.817

AC XY:

59989

AN XY:

73454

show subpopulations

African (AFR)

AF:

0.796

AC:

31987

AN:

40172

American (AMR)

AF:

0.793

AC:

12019

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.853

AC:

2945

AN:

3452

East Asian (EAS)

AF:

0.998

AC:

5140

AN:

5152

South Asian (SAS)

AF:

0.962

AC:

4641

AN:

4824

European-Finnish (FIN)

AF:

0.806

AC:

8542

AN:

10598

Middle Eastern (MID)

AF:

0.897

AC:

262

AN:

292

European-Non Finnish (NFE)

AF:

0.798

AC:

54045

AN:

67702

Other (OTH)

AF:

0.824

AC:

1726

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1266

2532

3799

5065

6331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.796

Hom.:

30492

Bravo

AF:

0.798

Asia WGS

AF:

0.957

AC:

3327

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.53

PhyloP100

-0.26

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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