Genetic Variant NM_001116.4:c.*2309G>A (chr16-3963466-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_001116.4(ADCY9):c.*2309G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 395,602 control chromosomes in the GnomAD database, including 57,497 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 0.45 ( 18590 hom., cov: 31)

Exomes 𝑓: 0.55 ( 38907 hom. )

Consequence

ADCY9
NM_001116.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

66 publications found

Variant links:

Genes affected

ADCY9 (HGNC:240): (adenylate cyclase 9) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [provided by RefSeq, Jul 2008]

ADCY9 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001116.4. 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
	ADCY9	NM_001116.4	MANE Select	c.*2309G>A		3_prime_UTR	Exon 11 of 11	NP_001107.2	O60503

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY9	ENST00000294016.8	TSL:1 MANE Select	c.*2309G>A	3_prime_UTR	Exon 11 of 11	ENSP00000294016.3	O60503
ADCY9	ENST00000936466.1		c.*2309G>A	3_prime_UTR	Exon 11 of 11	ENSP00000606525.1
ADCY9	ENST00000576936.5	TSL:5	c.567-9950G>A	intron	N/A	ENSP00000460066.1	I3L300

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69111

AN:

151876

Hom.:

18599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.481

GnomAD4 exome

AF:

0.553

AC:

134790

AN:

243608

Hom.:

38907

Cov.:

AF XY:

0.557

AC XY:

68878

AN XY:

123616

show subpopulations

African (AFR)

AF:

0.182

AC:

1281

AN:

7040

American (AMR)

AF:

0.382

AC:

2792

AN:

7308

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

4564

AN:

9094

East Asian (EAS)

AF:

0.335

AC:

7608

AN:

22694

South Asian (SAS)

AF:

0.361

AC:

1038

AN:

2874

European-Finnish (FIN)

AF:

0.576

AC:

12027

AN:

20896

Middle Eastern (MID)

AF:

0.496

AC:

636

AN:

1282

European-Non Finnish (NFE)

AF:

0.617

AC:

96506

AN:

156288

Other (OTH)

AF:

0.517

AC:

8338

AN:

16132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

2694

5388

8082

10776

13470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.455

AC:

69092

AN:

151994

Hom.:

18590

Cov.:

AF XY:

0.447

AC XY:

33221

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.184

AC:

7624

AN:

41458

American (AMR)

AF:

0.414

AC:

6314

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1810

AN:

3468

East Asian (EAS)

AF:

0.322

AC:

1657

AN:

5146

South Asian (SAS)

AF:

0.375

AC:

1809

AN:

4828

European-Finnish (FIN)

AF:

0.564

AC:

5950

AN:

10558

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42176

AN:

67962

Other (OTH)

AF:

0.476

AC:

1004

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1695

3390

5085

6780

8475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.550

Hom.:

79684

Bravo

AF:

0.431

Asia WGS

AF:

0.337

AC:

1172

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.6

(source)

DANN

Benign

0.83

PhyloP100

0.031

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

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