2-24897217-C-T

Variant names:

• chr2-24897217-C-T
• rs6752483
• NM_004036.5:c.675+21096G>A

Variant summary

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

The NM_004036.5(ADCY3):​c.675+21096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,150 control chromosomes in the GnomAD database, including 23,123 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 0.52 (23123 hom., cov: 28)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 18 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY3	NM_004036.5	c.675+21096G>A		intron_variant	Intron 2 of 21	ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY3	ENST00000679454.1	c.675+21096G>A		intron_variant	Intron 2 of 21		NM_004036.5	ENSP00000505261.1
ADCY3	ENST00000405392.6	c.675+21096G>A		intron_variant	Intron 1 of 20	1		ENSP00000384484.2
ADCY3	ENST00000260600.9	c.675+21096G>A		intron_variant	Intron 1 of 20	1		ENSP00000260600.5
ADCY3	ENST00000435135.5	c.675+21096G>A		intron_variant	Intron 2 of 7	5		ENSP00000389799.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79228 AN: 151032 Hom.: 23079 Cov.: 28

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.525 AC: 79316 AN: 151150 Hom.: 23123 Cov.: 28 AF XY: 0.517 AC XY: 38161 AN XY: 73820

African (AFR) AF: 0.798 AC: 32763 AN: 41074

American (AMR) AF: 0.376 AC: 5706 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1371 AN: 3456

East Asian (EAS) AF: 0.419 AC: 2131 AN: 5088

South Asian (SAS) AF: 0.457 AC: 2187 AN: 4782

European-Finnish (FIN) AF: 0.381 AC: 3991 AN: 10484

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29678 AN: 67800

Other (OTH) AF: 0.493 AC: 1030 AN: 2090

Alfa AF: 0.448 Hom.: 20162

Bravo AF: 0.535

Asia WGS AF: 0.434 AC: 1510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.23
PhyloP100		-2.1
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: rs6752483; hg19: chr2-25120086;