8-130990088-C-T

Position:

• chr8-130990088-C-T

Variant summary

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

The NM_001115.3(ADCY8):​c.1110+305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,142 control chromosomes in the GnomAD database, including 38,227 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 0.69 (38227 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

Genes affected

ADCY8 (HGNC:239): (adenylate cyclase 8) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. The enzymatic activity is under the control of several hormones, and different polypeptides participate in the transduction of the signal from the receptor to the catalytic moiety. Stimulatory or inhibitory receptors (Rs and Ri) interact with G proteins (Gs and Gi) that exhibit GTPase activity and they modulate the activity of the catalytic subunit of the adenylyl cyclase [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.1110+305G>A		intron_variant		ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.1110+305G>A		intron_variant		1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.1110+305G>A		intron_variant		1		ENSP00000367161.3
ADCY8	ENST00000522949.1	c.-46+351G>A		intron_variant		5		ENSP00000428010.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105494 AN: 152024 Hom.: 38178 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.694 AC: 105602 AN: 152142 Hom.: 38227 Cov.: 33 AF XY: 0.695 AC XY: 51716 AN XY: 74372

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.668

Alfa AF: 0.603 Hom.: 31188

Bravo AF: 0.710

Asia WGS AF: 0.781 AC: 2713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.66
DANN	Benign	0.37

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: rs3750889; hg19: chr8-132002334;