dbSNP rs2238432: ADCY9:c.*1635C>T (chr16-3964140-G-A) – 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.*1635C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,308 control chromosomes in the GnomAD database, including 1,652 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 0.11 ( 1652 hom., cov: 33)

Exomes 𝑓: 0.054 ( 0 hom. )

Consequence

ADCY9
NM_001116.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.720

Publications

11 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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.*1635C>T		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.*1635C>T	3_prime_UTR	Exon 11 of 11	ENSP00000294016.3	O60503
ADCY9	ENST00000936466.1		c.*1635C>T	3_prime_UTR	Exon 11 of 11	ENSP00000606525.1
ADCY9	ENST00000576936.5	TSL:5	c.566+10529C>T	intron	N/A	ENSP00000460066.1	I3L300

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15969

AN:

152098

Hom.:

1642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0731

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0946

GnomAD4 exome

AF:

0.0543

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0909

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0469

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.105

AC:

16011

AN:

152216

Hom.:

1652

Cov.:

AF XY:

0.104

AC XY:

7760

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.260

AC:

10781

AN:

41502

American (AMR)

AF:

0.0730

AC:

1117

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0830

AC:

288

AN:

3470

East Asian (EAS)

AF:

0.218

AC:

1125

AN:

5158

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4826

European-Finnish (FIN)

AF:

0.0209

AC:

222

AN:

10624

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0297

AC:

2022

AN:

68020

Other (OTH)

AF:

0.0978

AC:

207

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

661

1322

1983

2644

3305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0653

Hom.:

1259

Bravo

AF:

0.117

Asia WGS

AF:

0.144

AC:

501

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.73

PhyloP100

0.72

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)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over