rs2444217

Positions:

• chr16-3988386-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001116.4(ADCY9):​c.2310+608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 150,498 control chromosomes in the GnomAD database, including 17,704 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 0.46 (17704 hom., cov: 25)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY9	NM_001116.4	c.2310+608C>T		intron_variant		ENST00000294016.8
ADCY9	XM_005255079.4	c.2367+608C>T		intron_variant
ADCY9	XM_011522353.3	c.2367+608C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY9	ENST00000294016.8	c.2310+608C>T		intron_variant		1	NM_001116.4	P1
ADCY9	ENST00000576936.5	c.7+608C>T		intron_variant		5
ADCY9	ENST00000575550.5	n.520+608C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.457 AC: 68714 AN: 150382 Hom.: 17709 Cov.: 25

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.465

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 68706 AN: 150498 Hom.: 17704 Cov.: 25 AF XY: 0.457 AC XY: 33511 AN XY: 73360

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.460

Alfa AF: 0.548 Hom.: 44311

Bravo AF: 0.432

Asia WGS AF: 0.421 AC: 1461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs2444217; hg19: chr16-4038387;