NM_001115.3:c.3060+639C>T

Variant names:

• chr8-130799787-G-A
• rs263238
• NM_001115.3:c.3060+639C>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.3060+639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,200 control chromosomes in the GnomAD database, including 1,388 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 0.12 (1388 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.3060+639C>T		intron_variant	Intron 15 of 17	ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4	c.2970+639C>T		intron_variant	Intron 14 of 16		XP_005250826.1
ADCY8	XM_006716501.4	c.2862+639C>T		intron_variant	Intron 14 of 16		XP_006716564.1
ADCY8	XM_017013006.2	c.2772+639C>T		intron_variant	Intron 13 of 15		XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.3060+639C>T		intron_variant	Intron 15 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2667+639C>T		intron_variant	Intron 12 of 14	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18150 AN: 152082 Hom.: 1389 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.119 AC: 18149 AN: 152200 Hom.: 1388 Cov.: 33 AF XY: 0.124 AC XY: 9208 AN XY: 74390

African (AFR) AF: 0.0409 AC: 1698 AN: 41544

American (AMR) AF: 0.130 AC: 1984 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1513 AN: 5180

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4832

European-Finnish (FIN) AF: 0.155 AC: 1639 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9283 AN: 67996

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.132 Hom.: 5379

Bravo AF: 0.114

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.51
PhyloP100		-1.3
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: rs263238; hg19: chr8-131812033;