rs3730119

Positions:

• chr16-4007602-G-A
• chr16-4007602-G-C
• chr16-4007602-G-T

Variant summary

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

The NM_001116.4(ADCY9):​c.1694-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,514,218 control chromosomes in the GnomAD database, including 24,147 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 0.20 (3373 hom., cov: 31)
  • Exomes 𝑓: 0.17 (20774 hom.)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1694-44C>T		intron_variant		ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.1694-44C>T		intron_variant			XP_005255136.1
ADCY9	XM_011522353.3	c.1694-44C>T		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1694-44C>T		intron_variant		1	NM_001116.4	ENSP00000294016	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30420 AN: 151892 Hom.: 3364 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.199 AC: 40071 AN: 200898 Hom.: 4660 AF XY: 0.193 AC XY: 20901 AN XY: 108020

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.0903

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.168 AC: 229016 AN: 1362208 Hom.: 20774 Cov.: 21 AF XY: 0.168 AC XY: 113511 AN XY: 674196

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.200 AC: 30458 AN: 152010 Hom.: 3373 Cov.: 31 AF XY: 0.202 AC XY: 15035 AN XY: 74334

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.205

Alfa AF: 0.178 Hom.: 3611

Bravo AF: 0.214

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.7
DANN	Benign	0.82
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: rs3730119; hg19: chr16-4057603; COSMIC: COSV53571651;