16-4009438-T-C

Position:

• chr16-4009438-T-C

Variant summary

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

The NM_001116.4(ADCY9):​c.1694-1880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,948 control chromosomes in the GnomAD database, including 15,967 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 0.43 (15967 hom., cov: 32)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1694-1880A>G		intron_variant		ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.1694-1880A>G		intron_variant			XP_005255136.1
ADCY9	XM_011522353.3	c.1694-1880A>G		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1694-1880A>G		intron_variant		1	NM_001116.4	ENSP00000294016	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65310 AN: 151830 Hom.: 15964 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.430 AC: 65311 AN: 151948 Hom.: 15967 Cov.: 32 AF XY: 0.434 AC XY: 32216 AN XY: 74248

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.429

Alfa AF: 0.442 Hom.: 2050

Bravo AF: 0.409

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.86

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: rs2238448; hg19: chr16-4059439;