rs4678017

Variant names:

• chr3-123383176-A-C
• rs4678017
• NM_183357.3:c.1135-30595T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-123383176-A-C
• chr3-123383176-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183357.3(ADCY5):​c.1135-30595T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,666 control chromosomes in the GnomAD database, including 17,724 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 0.47 (17724 hom., cov: 31)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• dyskinesia with orofacial involvement, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with hyperkinetic movements and dyskinesia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial dyskinesia and facial myokymia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• choreatic disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY5	NM_183357.3	c.1135-30595T>G		intron_variant	Intron 1 of 20	ENST00000462833.6	NP_899200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6	c.1135-30595T>G		intron_variant	Intron 1 of 20	1	NM_183357.3	ENSP00000419361.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71748 AN: 151548 Hom.: 17710 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.473 AC: 71805 AN: 151666 Hom.: 17724 Cov.: 31 AF XY: 0.481 AC XY: 35613 AN XY: 74116

African (AFR) AF: 0.600 AC: 24782 AN: 41318

American (AMR) AF: 0.440 AC: 6712 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1648 AN: 3464

East Asian (EAS) AF: 0.682 AC: 3470 AN: 5090

South Asian (SAS) AF: 0.589 AC: 2830 AN: 4808

European-Finnish (FIN) AF: 0.464 AC: 4896 AN: 10548

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.381 AC: 25891 AN: 67882

Other (OTH) AF: 0.481 AC: 1011 AN: 2100

Alfa AF: 0.439 Hom.: 1936

Bravo AF: 0.478

Asia WGS AF: 0.687 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4678017; hg19: chr3-123102023;