rs753529

Positions:

• chr2-24831392-G-A
• chr2-24831392-G-C

Variant summary

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

The NM_004036.5(ADCY3):​c.2055+270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,984 control chromosomes in the GnomAD database, including 21,509 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 (21509 hom., cov: 32)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY3	NM_004036.5	c.2055+270C>T		intron_variant		ENST00000679454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY3	ENST00000679454.1	c.2055+270C>T		intron_variant			NM_004036.5	P4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78912 AN: 151866 Hom.: 21498 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.519 AC: 78943 AN: 151984 Hom.: 21509 Cov.: 32 AF XY: 0.521 AC XY: 38692 AN XY: 74278

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.567

Alfa AF: 0.558 Hom.: 5105

Bravo AF: 0.522

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.040
DANN	Benign	0.58

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: rs753529; hg19: chr2-25054261;