rs6545814

Positions:

• chr2-24908447-A-G
• chr2-24908447-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004036.5(ADCY3):​c.675+9866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,188 control chromosomes in the GnomAD database, including 22,884 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 (22884 hom., cov: 33)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY3	NM_004036.5	c.675+9866T>C		intron_variant		ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY3	ENST00000679454.1	c.675+9866T>C		intron_variant			NM_004036.5	ENSP00000505261	P4
ADCY3	ENST00000260600.9	c.675+9866T>C		intron_variant		1		ENSP00000260600	P4
ADCY3	ENST00000405392.6	c.675+9866T>C		intron_variant		1		ENSP00000384484	A1
ADCY3	ENST00000435135.5	c.675+9866T>C		intron_variant		5		ENSP00000389799

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79310 AN: 152070 Hom.: 22842 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.522 AC: 79395 AN: 152188 Hom.: 22884 Cov.: 33 AF XY: 0.514 AC XY: 38242 AN XY: 74394

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.489

Alfa AF: 0.446 Hom.: 13688

Bravo AF: 0.529

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs6545814; hg19: chr2-25131316;