NM_001115.3:c.960+16058G>A

Variant names:

• chr8-131023316-C-T
• rs1023096
• NM_001115.3:c.960+16058G>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.960+16058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,080 control chromosomes in the GnomAD database, including 37,293 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 0.68 (37293 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.960+16058G>A		intron_variant	Intron 1 of 17	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.960+16058G>A		intron_variant	Intron 1 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.960+16058G>A		intron_variant	Intron 1 of 14	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103921 AN: 151960 Hom.: 37236 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.684 AC: 104040 AN: 152080 Hom.: 37293 Cov.: 32 AF XY: 0.687 AC XY: 51042 AN XY: 74330

African (AFR) AF: 0.906 AC: 37594 AN: 41516

American (AMR) AF: 0.665 AC: 10160 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3468

East Asian (EAS) AF: 0.865 AC: 4472 AN: 5172

South Asian (SAS) AF: 0.732 AC: 3526 AN: 4816

European-Finnish (FIN) AF: 0.570 AC: 6021 AN: 10554

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.566 AC: 38461 AN: 67972

Other (OTH) AF: 0.654 AC: 1380 AN: 2110

Alfa AF: 0.606 Hom.: 14593

Bravo AF: 0.700

Asia WGS AF: 0.772 AC: 2683 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.46
PhyloP100		-0.90
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: rs1023096; hg19: chr8-132035562;