2-24874775-A-G

Variant names:

• chr2-24874775-A-G
• rs13407913
• NM_004036.5:c.676-2056T>C

Variant summary

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

The NM_004036.5(ADCY3):​c.676-2056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,080 control chromosomes in the GnomAD database, including 24,593 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 0.54 (24593 hom., cov: 33)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 50 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. 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.676-2056T>C		intron	N/A	NP_004027.2	O60266-1
	ADCY3	NM_001377128.1		c.676-2056T>C		intron	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.676-2056T>C		intron	N/A	NP_001307542.1	A0A0A0MSC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.676-2056T>C		intron	N/A	ENSP00000505261.1	O60266-1
	ADCY3	ENST00000405392.6	TSL:1	c.676-2056T>C		intron	N/A	ENSP00000384484.2	A0A0A0MSC1
	ADCY3	ENST00000260600.9	TSL:1	c.676-2056T>C		intron	N/A	ENSP00000260600.5	O60266-1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81738 AN: 151962 Hom.: 24545 Cov.: 33

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.538 AC: 81837 AN: 152080 Hom.: 24593 Cov.: 33 AF XY: 0.530 AC XY: 39411 AN XY: 74332

African (AFR) AF: 0.825 AC: 34252 AN: 41498

American (AMR) AF: 0.377 AC: 5756 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2423 AN: 5172

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4816

European-Finnish (FIN) AF: 0.397 AC: 4192 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29960 AN: 67960

Other (OTH) AF: 0.501 AC: 1058 AN: 2112

Alfa AF: 0.439 Hom.: 27059

Bravo AF: 0.546

Asia WGS AF: 0.476 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.55
DANN	Benign	0.67
PhyloP100		-0.69
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: rs13407913; hg19: chr2-25097644;