rs6798189

Positions:

• chr3-123376465-G-A

Variant summary

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

The NM_183357.3(ADCY5):​c.1135-23884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,978 control chromosomes in the GnomAD database, including 3,282 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 0.20 (3282 hom., cov: 31)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY5	NM_183357.3	c.1135-23884C>T		intron_variant		ENST00000462833.6	NP_899200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6	c.1135-23884C>T		intron_variant		1	NM_183357.3	ENSP00000419361	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29760 AN: 151860 Hom.: 3279 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.196 AC: 29772 AN: 151978 Hom.: 3282 Cov.: 31 AF XY: 0.193 AC XY: 14323 AN XY: 74282

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.174

Alfa AF: 0.232 Hom.: 5724

Bravo AF: 0.198

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.9
DANN	Benign	0.87

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: rs6798189; hg19: chr3-123095312;