rs2238426

Positions:

• chr16-3953732-A-G
• chr16-3953732-A-T

Variant summary

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

The ENST00000576936.5(ADCY9):​c.568-216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,170 control chromosomes in the GnomAD database, including 12,250 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 0.37 (12250 hom., cov: 33)
• Consequence: ADCY9 ENST00000576936.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837

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 (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY9	XM_011522353.3	c.2928-216T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY9	ENST00000576936.5	c.568-216T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56999 AN: 152052 Hom.: 12254 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.375 AC: 56988 AN: 152170 Hom.: 12250 Cov.: 33 AF XY: 0.373 AC XY: 27734 AN XY: 74376

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.378

Alfa AF: 0.387 Hom.: 1828

Bravo AF: 0.362

Asia WGS AF: 0.341 AC: 1184 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	4.4
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2238426; hg19: chr16-4003733;