rs10505568

Variant names:

• chr8-131025304-A-C
• rs10505568
• NM_001115.3:c.960+14070T>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.960+14070T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,228 control chromosomes in the GnomAD database, including 509 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 0.062 (509 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 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.960+14070T>G		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.960+14070T>G		intron	N/A	ENSP00000286355.5	P40145
	ADCY8	ENST00000377928.7	TSL:1	c.960+14070T>G		intron	N/A	ENSP00000367161.3	E7EVL1
	ADCY8	ENST00000912159.1		c.960+14070T>G		intron	N/A	ENSP00000582218.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9432 AN: 152110 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0619 AC: 9426 AN: 152228 Hom.: 509 Cov.: 32 AF XY: 0.0655 AC XY: 4875 AN XY: 74416

African (AFR) AF: 0.0340 AC: 1413 AN: 41566

American (AMR) AF: 0.0306 AC: 468 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 138 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1556 AN: 5162

South Asian (SAS) AF: 0.165 AC: 797 AN: 4820

European-Finnish (FIN) AF: 0.0835 AC: 885 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0593 AC: 4031 AN: 68014

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0586 Hom.: 1024

Bravo AF: 0.0562

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		3.0
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: rs10505568; hg19: chr8-132037550;