rs965814

Variant names:

• chr8-130882637-G-A
• rs965814
• NM_001115.3:c.2109+1927C>T

Variant summary

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

The NM_001115.3(ADCY8):​c.2109+1927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,052 control chromosomes in the GnomAD database, including 18,002 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 0.45 (18002 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 4 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]

ENSG00000302847 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.2109+1927C>T		intron_variant	Intron 8 of 17	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.2109+1927C>T		intron_variant	Intron 8 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2109+1927C>T		intron_variant	Intron 8 of 14	1		ENSP00000367161.3
ENSG00000302847	ENST00000789998.1	n.252-24278G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68805 AN: 151934 Hom.: 17955 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.453 AC: 68919 AN: 152052 Hom.: 18002 Cov.: 32 AF XY: 0.449 AC XY: 33385 AN XY: 74332

African (AFR) AF: 0.731 AC: 30355 AN: 41508

American (AMR) AF: 0.377 AC: 5753 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1056 AN: 5156

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10564

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23765 AN: 67952

Other (OTH) AF: 0.440 AC: 927 AN: 2108

Alfa AF: 0.380 Hom.: 45242

Bravo AF: 0.469

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.34
PhyloP100		0.13
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: rs965814; hg19: chr8-131894883; COSMIC: COSV107264170;