8-130877924-G-A

Position:

• chr8-130877924-G-A

Variant summary

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

The NM_001115.3(ADCY8):​c.2109+6640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,934 control chromosomes in the GnomAD database, including 25,795 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 0.58 (25795 hom., cov: 31)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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]

LOC105375762 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.2109+6640C>T		intron_variant		ENST00000286355.10	NP_001106.1
LOC105375762	XR_928658.2	n.145-5733G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.2109+6640C>T		intron_variant		1	NM_001115.3	ENSP00000286355	P1
ADCY8	ENST00000377928.7	c.2109+6640C>T		intron_variant		1		ENSP00000367161

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87539 AN: 151816 Hom.: 25771 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.577 AC: 87605 AN: 151934 Hom.: 25795 Cov.: 31 AF XY: 0.577 AC XY: 42799 AN XY: 74234

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.575

Alfa AF: 0.534 Hom.: 29659

Bravo AF: 0.590

Asia WGS AF: 0.480 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.69

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: rs7842798; hg19: chr8-131890170;