chr8-130866822-A-C

Variant names:

• chr8-130866822-A-C
• rs10505566
• NM_001115.3:c.2210+1024T>G

Variant summary

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

The NM_001115.3(ADCY8):​c.2210+1024T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,090 control chromosomes in the GnomAD database, including 2,442 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 0.16 (2442 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• 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]

ENSG00000302847 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.2210+1024T>G		intron_variant	Intron 9 of 17	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.2210+1024T>G		intron_variant	Intron 9 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2109+17742T>G		intron_variant	Intron 8 of 14	1		ENSP00000367161.3
ENSG00000302847	ENST00000789998.1	n.251+15743A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24862 AN: 151972 Hom.: 2442 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.164 AC: 24870 AN: 152090 Hom.: 2442 Cov.: 32 AF XY: 0.160 AC XY: 11858 AN XY: 74340

African (AFR) AF: 0.0497 AC: 2065 AN: 41538

American (AMR) AF: 0.195 AC: 2984 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.181 AC: 932 AN: 5148

South Asian (SAS) AF: 0.125 AC: 603 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2027 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15104 AN: 67940

Other (OTH) AF: 0.145 AC: 306 AN: 2114

Alfa AF: 0.192 Hom.: 9208

Bravo AF: 0.157

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		0.18
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: rs10505566; hg19: chr8-131879068;