16-4015582-A-G

Variant names:

• chr16-4015582-A-G
• rs1967309
• NM_001116.4:c.1694-8024T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000294016.8(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 ENST00000294016.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000294016.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY9	NM_001116.4	MANE Select	c.1694-8024T>C		intron	N/A	NP_001107.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY9	ENST00000294016.8	TSL:1 MANE Select	c.1694-8024T>C		intron	N/A	ENSP00000294016.3
	ADCY9	ENST00000575550.5	TSL:4	n.101T>C		non_coding_transcript_exon	Exon 1 of 5
	ADCY9	ENST00000572288.1	TSL:4	c.278-8024T>C		intron	N/A	ENSP00000461825.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 6 AN: 12

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.337 AC: 13961 AN: 41426

American (AMR) AF: 0.473 AC: 7222 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2026 AN: 3466

East Asian (EAS) AF: 0.574 AC: 2957 AN: 5156

South Asian (SAS) AF: 0.478 AC: 2304 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6671 AN: 10542

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40433 AN: 67968

Other (OTH) AF: 0.498 AC: 1049 AN: 2108

Alfa AF: 0.566 Hom.: 50243

Bravo AF: 0.491

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.54
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1967309; hg19: chr16-4065583;