Variant rs6806529 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 ENST00000462833.6(ADCY5):c.1519-75T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,502,588 control chromosomes in the GnomAD database, including 264,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29587 hom., cov: 35)

Exomes 𝑓: 0.59 ( 235219 hom. )

Consequence

ADCY5
ENST00000462833.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.468

Variant links:

Genes affected

ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ADCY5 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=-0.58).

BP6

Variant 3-123331091-A-C is Benign according to our data. Variant chr3-123331091-A-C is described in ClinVar as [Benign]. Clinvar id is 1189009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY5	NM_183357.3 linkuse as main transcript	c.1519-75T>G		intron_variant		ENST00000462833.6	NP_899200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6 linkuse as main transcript	c.1519-75T>G		intron_variant		1	NM_183357.3	ENSP00000419361	P1	O95622-1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93832

AN:

152088

Hom.:

29558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.585

AC:

790392

AN:

1350382

Hom.:

235219

AF XY:

0.588

AC XY:

393652

AN XY:

669898

show subpopulations

Gnomad4 AFR exome

AF:

0.687

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.593

Gnomad4 EAS exome

AF:

0.971

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.569

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.617

AC:

93904

AN:

152206

Hom.:

29587

Cov.:

AF XY:

0.619

AC XY:

46033

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.529

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.956

Gnomad4 SAS

AF:

0.673

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.572

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.588

Hom.:

34348

Bravo

AF:

0.617

Asia WGS

AF:

0.799

AC:

2775

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	GeneDx	Jul 30, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 62. Only high quality variants are reported. -

Dyskinesia with orofacial involvement, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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