rs1968482

Variant names:

• chr2-24863989-T-C
• rs1968482
• NM_004036.5:c.825+8581A>G

Variant summary

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

The NM_004036.5(ADCY3):​c.825+8581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,148 control chromosomes in the GnomAD database, including 8,197 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 0.33 (8197 hom., cov: 33)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY3	NM_004036.5	c.825+8581A>G		intron_variant	Intron 3 of 21	ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY3	ENST00000679454.1	c.825+8581A>G		intron_variant	Intron 3 of 21		NM_004036.5	ENSP00000505261.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49424 AN: 152030 Hom.: 8196 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.325 AC: 49462 AN: 152148 Hom.: 8197 Cov.: 33 AF XY: 0.325 AC XY: 24152 AN XY: 74388

African (AFR) AF: 0.343 AC: 14239 AN: 41508

American (AMR) AF: 0.232 AC: 3547 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1917 AN: 5168

South Asian (SAS) AF: 0.396 AC: 1914 AN: 4828

European-Finnish (FIN) AF: 0.335 AC: 3552 AN: 10594

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22183 AN: 67992

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.322 Hom.: 3413

Bravo AF: 0.315

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		1.1
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: rs1968482; hg19: chr2-25086858;