rs2384061

Variant names:

• chr2-24912751-G-A
• rs2384061
• NM_004036.5:c.675+5562C>T

Variant summary

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

The NM_001377128.1(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_001377128.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 36 publications found

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]

ADCY3 Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377128.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	NM_004036.5	MANE Select	c.675+5562C>T		intron	N/A	NP_004027.2
	ADCY3	NM_001377128.1		c.675+5562C>T		intron	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.675+5562C>T		intron	N/A	NP_001307542.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.675+5562C>T		intron	N/A	ENSP00000505261.1
	ADCY3	ENST00000405392.6	TSL:1	c.675+5562C>T		intron	N/A	ENSP00000384484.2
	ADCY3	ENST00000260600.9	TSL:1	c.675+5562C>T		intron	N/A	ENSP00000260600.5

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

African (AFR) AF: 0.555 AC: 23013 AN: 41446

American (AMR) AF: 0.327 AC: 4995 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2173 AN: 5178

South Asian (SAS) AF: 0.411 AC: 1980 AN: 4812

European-Finnish (FIN) AF: 0.376 AC: 3970 AN: 10554

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28298 AN: 67966

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.416 Hom.: 27989

Bravo AF: 0.440

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2384061; hg19: chr2-25135620;