rs263238

chr8-130799787-G-Achr8-130799787-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.3060+639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,200 control chromosomes in the GnomAD database, including 1,388 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 0.12 (1388 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY8	NM_001115.3	c.3060+639C>T		intron_variant		ENST00000286355.10
ADCY8	XM_005250769.4	c.2970+639C>T		intron_variant
ADCY8	XM_006716501.4	c.2862+639C>T		intron_variant
ADCY8	XM_017013006.2	c.2772+639C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY8	ENST00000286355.10	c.3060+639C>T		intron_variant		1	NM_001115.3	P1
ADCY8	ENST00000377928.7	c.2667+639C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18150 AN: 152082 Hom.: 1389 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.119 AC: 18149 AN: 152200 Hom.: 1388 Cov.: 33 AF XY: 0.124 AC XY: 9208 AN XY: 74390

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.117

Alfa AF: 0.136 Hom.: 3642

Bravo AF: 0.114

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.51
Dann	Benign	0.51

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: rs263238; hg19: chr8-131812033;