chr3-123412407-C-T

Position:

• chr3-123412407-C-T

Variant summary

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

The ENST00000462833.6(ADCY5):​c.1134+35005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,186 control chromosomes in the GnomAD database, including 3,403 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 (3403 hom., cov: 32)
• Consequence: ADCY5 ENST00000462833.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY5	NM_183357.3	c.1134+35005G>A		intron_variant		ENST00000462833.6	NP_899200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6	c.1134+35005G>A		intron_variant		1	NM_183357.3	ENSP00000419361.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30329 AN: 152068 Hom.: 3400 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.199 AC: 30343 AN: 152186 Hom.: 3403 Cov.: 32 AF XY: 0.196 AC XY: 14609 AN XY: 74434

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.176

Alfa AF: 0.216 Hom.: 2725

Bravo AF: 0.200

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.45

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: rs17361324; hg19: chr3-123131254;