rs6986982

Positions:

• chr8-130975129-G-A
• chr8-130975129-G-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+15264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,060 control chromosomes in the GnomAD database, including 5,769 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 0.24 (5769 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY8	NM_001115.3	c.1110+15264C>T		intron_variant		ENST00000286355.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY8	ENST00000286355.10	c.1110+15264C>T		intron_variant		1	NM_001115.3	P1
ADCY8	ENST00000377928.7	c.1110+15264C>T		intron_variant		1
ADCY8	ENST00000522949.1	c.-46+15310C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35847 AN: 151940 Hom.: 5762 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.236 AC: 35872 AN: 152060 Hom.: 5769 Cov.: 33 AF XY: 0.229 AC XY: 17041 AN XY: 74362

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.229

Alfa AF: 0.169 Hom.: 3514

Bravo AF: 0.255

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.75

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: rs6986982; hg19: chr8-131987375;