Variant rs7604576 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.187

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
ADCY3	NM_004036.5 linkuse as main transcript	c.2578-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ADCY3	ENST00000679454.1 linkuse as main transcript	c.2578-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_004036.5	ENSP00000505261	P4	O60266-1
ADCY3	ENST00000260600.9 linkuse as main transcript	c.2578-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000260600	P4	O60266-1
ADCY3	ENST00000405392.6 linkuse as main transcript	c.2581-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000384484	A1
ADCY3	ENST00000606682.5 linkuse as main transcript	c.1519-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000475652

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73490

AN:

152050

Hom.:

18939

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.532

AC XY:

386487

AN XY:

726860

show subpopulations

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.:

AF XY:

0.488

AC XY:

36333

AN XY:

74398

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over