rs2384061

Positions:

• chr2-24912751-G-A

Variant summary

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

The NM_004036.5(ADCY3):​c.675+5562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,002 control chromosomes in the GnomAD database, including 15,336 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 0.44 (15336 hom., cov: 32)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY3	NM_004036.5	c.675+5562C>T		intron_variant		ENST00000679454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY3	ENST00000679454.1	c.675+5562C>T		intron_variant			NM_004036.5	P4
ADCY3	ENST00000260600.9	c.675+5562C>T		intron_variant		1		P4
ADCY3	ENST00000405392.6	c.675+5562C>T		intron_variant		1		A1
ADCY3	ENST00000435135.5	c.675+5562C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67043 AN: 151884 Hom.: 15323 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.441 AC: 67089 AN: 152002 Hom.: 15336 Cov.: 32 AF XY: 0.436 AC XY: 32382 AN XY: 74280

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.426

Alfa AF: 0.412 Hom.: 8147

Bravo AF: 0.440

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.68

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: rs2384061; hg19: chr2-25135620;