8-131032693-T-C

Variant names:

• chr8-131032693-T-C
• rs913819
• NM_001115.3:c.960+6681A>G

Variant summary

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

The ENST00000286355.10(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 ENST00000286355.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000286355.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	NM_001115.3	MANE Select	c.960+6681A>G		intron	N/A	NP_001106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	ENST00000286355.10	TSL:1 MANE Select	c.960+6681A>G		intron	N/A	ENSP00000286355.5
	ADCY8	ENST00000377928.7	TSL:1	c.960+6681A>G		intron	N/A	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

African (AFR) AF: 0.304 AC: 12609 AN: 41468

American (AMR) AF: 0.456 AC: 6955 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3274 AN: 5150

South Asian (SAS) AF: 0.547 AC: 2632 AN: 4816

European-Finnish (FIN) AF: 0.487 AC: 5156 AN: 10590

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30161 AN: 67960

Other (OTH) AF: 0.419 AC: 880 AN: 2102

Alfa AF: 0.432 Hom.: 6037

Bravo AF: 0.407

Asia WGS AF: 0.568 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.27
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: rs913819; hg19: chr8-132044939;