Variant 16-3966843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001116.4(ADCY9):c.2994C>T(p.Arg998=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,614,182 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 80 hom. )

Consequence

ADCY9
NM_001116.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.50

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-3966843-G-A is Benign according to our data. Variant chr16-3966843-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.5 with no splicing effect.

BS2

High AC in GnomAd4 at 957 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADCY9	NM_001116.4 linkuse as main transcript	c.2994C>T	p.Arg998=	synonymous_variant	11/11	ENST00000294016.8
ADCY9	XM_005255079.4 linkuse as main transcript	c.3051C>T	p.Arg1017=	synonymous_variant	11/11
ADCY9	XM_011522353.3 linkuse as main transcript	c.2927+7826C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY9	ENST00000294016.8 linkuse as main transcript	c.2994C>T	p.Arg998=	synonymous_variant	11/11	1	NM_001116.4	P1
ADCY9	ENST00000576936.5 linkuse as main transcript	c.567+7826C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

957

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00584

AC:

1469

AN:

251418

Hom.:

AF XY:

0.00586

AC XY:

796

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00923

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00969

AC:

14161

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00941

AC XY:

6842

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00402

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00238

Gnomad4 FIN exome

AF:

0.00245

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00987

GnomAD4 genome

AF:

0.00628

AC:

957

AN:

152316

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00817

Hom.:

Bravo

AF:

0.00698

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00942

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ADCY9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

DANN

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over