rs263249

Positions:

• chr8-130783014-A-G
• chr8-130783014-A-T

Variant summary

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

The NM_001115.3(ADCY8):​c.3268+677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,070 control chromosomes in the GnomAD database, including 35,555 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 0.67 (35555 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY8	NM_001115.3	c.3268+677T>C		intron_variant		ENST00000286355.10
ADCY8	XM_005250769.4	c.3178+677T>C		intron_variant
ADCY8	XM_006716501.4	c.3070+677T>C		intron_variant
ADCY8	XM_017013006.2	c.2980+677T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY8	ENST00000286355.10	c.3268+677T>C		intron_variant		1	NM_001115.3	P1
ADCY8	ENST00000377928.7	c.2875+677T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102366 AN: 151952 Hom.: 35534 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.674 AC: 102437 AN: 152070 Hom.: 35555 Cov.: 32 AF XY: 0.659 AC XY: 48937 AN XY: 74308

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.658

Alfa AF: 0.703 Hom.: 5978

Bravo AF: 0.686

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.77

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: rs263249; hg19: chr8-131795260;