rs2531995

Positions:

• chr16-3963466-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.*2309G>A		3_prime_UTR_variant	11/11	ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.*2309G>A		3_prime_UTR_variant	11/11		XP_005255136.1
ADCY9	XM_011522353.3	c.2928-9950G>A		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.*2309G>A		3_prime_UTR_variant	11/11	1	NM_001116.4	ENSP00000294016.3
ADCY9	ENST00000576936.5	c.567-9950G>A		intron_variant		5		ENSP00000460066.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69111 AN: 151876 Hom.: 18599 Cov.: 31

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.: 0 AF XY: 0.557 AC XY: 68878 AN XY: 123616

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.455 AC: 69092 AN: 151994 Hom.: 18590 Cov.: 31 AF XY: 0.447 AC XY: 33221 AN XY: 74298

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.476

Alfa AF: 0.571 Hom.: 36347

Bravo AF: 0.431

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2531995; hg19: chr16-4013467; COSMIC: COSV53581083;