Genetic Variant NM_001012302.3: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:

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=-0.88).

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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