rs6470863

Positions:

• chr8-130934570-A-G

Variant summary

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

The NM_001115.3(ADCY8):​c.1481+2503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,138 control chromosomes in the GnomAD database, including 2,233 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 0.17 (2233 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.1481+2503T>C		intron_variant		ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.1481+2503T>C		intron_variant		1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.1481+2503T>C		intron_variant		1		ENSP00000367161.3
ADCY8	ENST00000522949.1	c.326+2503T>C		intron_variant		5		ENSP00000428010.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25534 AN: 152020 Hom.: 2224 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.168 AC: 25579 AN: 152138 Hom.: 2233 Cov.: 32 AF XY: 0.163 AC XY: 12152 AN XY: 74420

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0917

Gnomad4 EAS AF: 0.0636

Gnomad4 SAS AF: 0.0977

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.132

Alfa AF: 0.165 Hom.: 1031

Bravo AF: 0.168

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.53

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: rs6470863; hg19: chr8-131946816;