rs7842798

Variant names:

• chr8-130877924-G-A
• rs7842798
• NM_001115.3:c.2109+6640C>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+6640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,934 control chromosomes in the GnomAD database, including 25,795 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 0.58 (25795 hom., cov: 31)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.2109+6640C>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+6640C>T		intron_variant	Intron 8 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2109+6640C>T		intron_variant	Intron 8 of 14	1		ENSP00000367161.3
ENSG00000302847	ENST00000789998.1	n.251+26845G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87539 AN: 151816 Hom.: 25771 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.577 AC: 87605 AN: 151934 Hom.: 25795 Cov.: 31 AF XY: 0.577 AC XY: 42799 AN XY: 74234

African (AFR) AF: 0.700 AC: 29002 AN: 41426

American (AMR) AF: 0.565 AC: 8623 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1957 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3269 AN: 5136

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4824

European-Finnish (FIN) AF: 0.545 AC: 5739 AN: 10530

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35282 AN: 67966

Other (OTH) AF: 0.575 AC: 1214 AN: 2112

Alfa AF: 0.540 Hom.: 38398

Bravo AF: 0.590

Asia WGS AF: 0.480 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.69
PhyloP100		-0.061
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: rs7842798; hg19: chr8-131890170;