rs11717195

chr3-123363551-T-C

Variant summary

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

The NM_183357.3(ADCY5):c.1135-10970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,230 control chromosomes in the GnomAD database, including 2,919 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 0.18 (2919 hom., cov: 33)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY5	NM_183357.3	c.1135-10970A>G		intron_variant		ENST00000462833.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY5	ENST00000462833.6	c.1135-10970A>G		intron_variant		1	NM_183357.3	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28088 AN: 152112 Hom.: 2916 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.185 AC: 28100 AN: 152230 Hom.: 2919 Cov.: 33 AF XY: 0.182 AC XY: 13525 AN XY: 74416

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.157

Alfa AF: 0.205 Hom.: 562

Bravo AF: 0.186

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.52
Dann	Benign	0.71

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: rs11717195; hg19: chr3-123082398;