8-130990088-C-T

Variant names:

• chr8-130990088-C-T
• rs3750889
• NM_001115.3:c.1110+305G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001115.3(ADCY8):​c.1110+305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,142 control chromosomes in the GnomAD database, including 38,227 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 0.69 (38227 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	NM_001115.3	MANE Select	c.1110+305G>A		intron	N/A	NP_001106.1	P40145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	ENST00000286355.10	TSL:1 MANE Select	c.1110+305G>A		intron	N/A	ENSP00000286355.5	P40145
	ADCY8	ENST00000377928.7	TSL:1	c.1110+305G>A		intron	N/A	ENSP00000367161.3	E7EVL1
	ADCY8	ENST00000912159.1		c.1110+305G>A		intron	N/A	ENSP00000582218.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105494 AN: 152024 Hom.: 38178 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.694 AC: 105602 AN: 152142 Hom.: 38227 Cov.: 33 AF XY: 0.695 AC XY: 51716 AN XY: 74372

African (AFR) AF: 0.907 AC: 37690 AN: 41546

American (AMR) AF: 0.679 AC: 10373 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2000 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4501 AN: 5186

South Asian (SAS) AF: 0.720 AC: 3467 AN: 4816

European-Finnish (FIN) AF: 0.580 AC: 6125 AN: 10568

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39530 AN: 67956

Other (OTH) AF: 0.668 AC: 1412 AN: 2114

Alfa AF: 0.637 Hom.: 52145

Bravo AF: 0.710

Asia WGS AF: 0.781 AC: 2713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.66
DANN	Benign	0.37
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3750889; hg19: chr8-132002334;