8-131032693-T-C

Position:

• chr8-131032693-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001115.3(ADCY8):​c.960+6681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,020 control chromosomes in the GnomAD database, including 13,750 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 0.42 (13750 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.960+6681A>G		intron_variant		ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.960+6681A>G		intron_variant		1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.960+6681A>G		intron_variant		1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63390 AN: 151902 Hom.: 13750 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.417 AC: 63413 AN: 152020 Hom.: 13750 Cov.: 32 AF XY: 0.425 AC XY: 31586 AN XY: 74312

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.419

Alfa AF: 0.428 Hom.: 3917

Bravo AF: 0.407

Asia WGS AF: 0.568 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs913819; hg19: chr8-132044939;