rs6545800

Variant names:

• chr2-24896016-C-T
• rs6545800
• NM_004036.5:c.675+22297G>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+22297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,026 control chromosomes in the GnomAD database, including 23,345 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 0.53 (23345 hom., cov: 32)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 49 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY3	NM_004036.5	c.675+22297G>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+22297G>A		intron_variant	Intron 2 of 21		NM_004036.5	ENSP00000505261.1
ADCY3	ENST00000405392.6	c.675+22297G>A		intron_variant	Intron 1 of 20	1		ENSP00000384484.2
ADCY3	ENST00000260600.9	c.675+22297G>A		intron_variant	Intron 1 of 20	1		ENSP00000260600.5
ADCY3	ENST00000435135.5	c.675+22297G>A		intron_variant	Intron 2 of 7	5		ENSP00000389799.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79874 AN: 151908 Hom.: 23301 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.526 AC: 79962 AN: 152026 Hom.: 23345 Cov.: 32 AF XY: 0.518 AC XY: 38503 AN XY: 74298

African (AFR) AF: 0.798 AC: 33119 AN: 41480

American (AMR) AF: 0.377 AC: 5763 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2173 AN: 5174

South Asian (SAS) AF: 0.459 AC: 2210 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4034 AN: 10548

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

European-Non Finnish (NFE) AF: 0.438 AC: 29786 AN: 67946

Other (OTH) AF: 0.492 AC: 1040 AN: 2112

Alfa AF: 0.482 Hom.: 30690

Bravo AF: 0.535

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.48
PhyloP100		-0.21
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: rs6545800; hg19: chr2-25118885;