rs7604576

chr2-24824539-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004036.5(ADCY3):c.2578-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,613,354 control chromosomes in the GnomAD database, including 228,070 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18952 hom., cov: 33)
  • Exomes 𝑓: 0.53 (209118 hom.)
• Consequence: ADCY3 NM_004036.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003597
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.187

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-24824539-A-G is Benign according to our data. Variant chr2-24824539-A-G is described in ClinVar as [Benign]. Clinvar id is 1598739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY3	NM_004036.5	c.2578-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000679454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY3	ENST00000679454.1	c.2578-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_004036.5	P4
ADCY3	ENST00000260600.9	c.2578-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P4
ADCY3	ENST00000405392.6	c.2581-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		A1
ADCY3	ENST00000606682.5	c.1519-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73490 AN: 152050 Hom.: 18939 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.508

GnomAD3 exomes AF: 0.551 AC: 138427 AN: 251200 Hom.: 39709 AF XY: 0.548 AC XY: 74378 AN XY: 135758

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.639

Gnomad SAS exome AF: 0.571

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.557

GnomAD4 exome AF: 0.531 AC: 775992 AN: 1461186 Hom.: 209118 Cov.: 43 AF XY: 0.532 AC XY: 386487 AN XY: 726860

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.483 AC: 73518 AN: 152168 Hom.: 18952 Cov.: 33 AF XY: 0.488 AC XY: 36333 AN XY: 74398

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.513

Alfa AF: 0.505 Hom.: 9410

Bravo AF: 0.486

Asia WGS AF: 0.645 AC: 2242 AN: 3478

EpiCase AF: 0.516

EpiControl AF: 0.528

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.2
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
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: rs7604576; hg19: chr2-25047408; COSMIC: COSV53165736; COSMIC: COSV53165736;