chr8-131009717-G-A

Variant names:

• chr8-131009717-G-A
• rs1411187
• NM_001115.3:c.961-19175C>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.961-19175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,192 control chromosomes in the GnomAD database, including 30,048 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 0.61 (30048 hom., cov: 34)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.961-19175C>T		intron_variant	Intron 1 of 17	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.961-19175C>T		intron_variant	Intron 1 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.961-19175C>T		intron_variant	Intron 1 of 14	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92356 AN: 152072 Hom.: 29997 Cov.: 34

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.608 AC: 92473 AN: 152192 Hom.: 30048 Cov.: 34 AF XY: 0.611 AC XY: 45466 AN XY: 74394

African (AFR) AF: 0.844 AC: 35084 AN: 41546

American (AMR) AF: 0.561 AC: 8578 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4044 AN: 5186

South Asian (SAS) AF: 0.636 AC: 3068 AN: 4822

European-Finnish (FIN) AF: 0.524 AC: 5540 AN: 10576

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33123 AN: 67996

Other (OTH) AF: 0.558 AC: 1179 AN: 2112

Alfa AF: 0.534 Hom.: 15588

Bravo AF: 0.618

Asia WGS AF: 0.698 AC: 2423 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.0060
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: rs1411187; hg19: chr8-132021963;