Genetic Variant ANO9:c.833-7G>A (chr11-429659-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.833-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,612,230 control chromosomes in the GnomAD database, including 278,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 25442 hom., cov: 33)

Exomes 𝑓: 0.59 ( 253124 hom. )

Consequence

ANO9
NM_001012302.3 splice_region, intron

Scores

Splicing: ADA: 0.00008639

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.20

Publications

34 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012302.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO9	NM_001012302.3	MANE Select	c.833-7G>A		splice_region intron	N/A	NP_001012302.2	A1A5B4-1
	ANO9	NM_001347882.2		c.401-7G>A		splice_region intron	N/A	NP_001334811.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO9	ENST00000332826.7	TSL:1 MANE Select	c.833-7G>A	splice_region intron	N/A	ENSP00000332788.6	A1A5B4-1
ANO9	ENST00000528927.5	TSL:1	n.944-7G>A	splice_region intron	N/A
ANO9	ENST00000884108.1		c.974-7G>A	splice_region intron	N/A	ENSP00000554167.1

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87516

AN:

151938

Hom.:

25415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.582

GnomAD2 exomes

AF:

0.558

AC:

138644

AN:

248374

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.601

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.586

AC:

856348

AN:

1460174

Hom.:

253124

Cov.:

AF XY:

0.586

AC XY:

425885

AN XY:

726394

show subpopulations

African (AFR)

AF:

0.563

AC:

18850

AN:

33476

American (AMR)

AF:

0.503

AC:

22455

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

15383

AN:

26114

East Asian (EAS)

AF:

0.349

AC:

13861

AN:

39688

South Asian (SAS)

AF:

0.576

AC:

49642

AN:

86250

European-Finnish (FIN)

AF:

0.565

AC:

29398

AN:

52036

Middle Eastern (MID)

AF:

0.637

AC:

3675

AN:

5766

European-Non Finnish (NFE)

AF:

0.600

AC:

667598

AN:

1111820

Other (OTH)

AF:

0.588

AC:

35486

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

24602

49204

73805

98407

123009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18032

36064

54096

72128

90160

<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:

0.576

AC:

87581

AN:

152056

Hom.:

25442

Cov.:

AF XY:

0.573

AC XY:

42609

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.569

AC:

23584

AN:

41468

American (AMR)

AF:

0.552

AC:

8451

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2063

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1926

AN:

5160

South Asian (SAS)

AF:

0.559

AC:

2700

AN:

4826

European-Finnish (FIN)

AF:

0.565

AC:

5975

AN:

10578

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.603

AC:

40954

AN:

67946

Other (OTH)

AF:

0.585

AC:

1235

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1899

3798

5698

7597

9496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.591

Hom.:

74075

Bravo

AF:

0.571

Asia WGS

AF:

0.480

AC:

1671

AN:

3478

EpiCase

AF:

0.605

EpiControl

AF:

0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.60

(source)

DANN

Benign

0.52

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over