rs1967309

Positions:

• chr16-4015582-A-G
• chr16-4015582-A-T

Variant summary

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

The NM_001116.4(ADCY9):​c.1694-8024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,982 control chromosomes in the GnomAD database, including 20,763 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 0.51 (20761 hom., cov: 31)
  • Exomes 𝑓: 0.56 (2 hom.)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1694-8024T>C		intron_variant		ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.1694-8024T>C		intron_variant			XP_005255136.1
ADCY9	XM_011522353.3	c.1694-8024T>C		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1694-8024T>C		intron_variant		1	NM_001116.4	ENSP00000294016	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77317 AN: 151846 Hom.: 20753 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.509 AC: 77335 AN: 151964 Hom.: 20761 Cov.: 31 AF XY: 0.512 AC XY: 38035 AN XY: 74264

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.498

Alfa AF: 0.566 Hom.: 14115

Bravo AF: 0.491

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1967309; hg19: chr16-4065583;