rs10505568

Positions:

• chr8-131025304-A-C

Variant summary

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

The NM_001115.3(ADCY8):​c.960+14070T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,228 control chromosomes in the GnomAD database, including 509 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 0.062 (509 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.960+14070T>G		intron_variant		ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.960+14070T>G		intron_variant		1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.960+14070T>G		intron_variant		1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9432 AN: 152110 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0619 AC: 9426 AN: 152228 Hom.: 509 Cov.: 32 AF XY: 0.0655 AC XY: 4875 AN XY: 74416

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0580 Hom.: 416

Bravo AF: 0.0562

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.64

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: rs10505568; hg19: chr8-132037550;