rs1369450

Variant names:

• chr8-130880476-A-C
• rs1369450
• NM_001115.3:c.2109+4088T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-130880476-A-C
• chr8-130880476-A-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.2109+4088T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,080 control chromosomes in the GnomAD database, including 20,092 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 0.51 (20092 hom., cov: 33)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• 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]

ENSG00000302847 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.2109+4088T>G		intron_variant	Intron 8 of 17	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.2109+4088T>G		intron_variant	Intron 8 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2109+4088T>G		intron_variant	Intron 8 of 14	1		ENSP00000367161.3
ENSG00000302847	ENST00000789998.1	n.252-26439A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77894 AN: 151962 Hom.: 20084 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.512 AC: 77937 AN: 152080 Hom.: 20092 Cov.: 33 AF XY: 0.515 AC XY: 38262 AN XY: 74328

African (AFR) AF: 0.473 AC: 19615 AN: 41492

American (AMR) AF: 0.538 AC: 8220 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1967 AN: 3466

East Asian (EAS) AF: 0.636 AC: 3288 AN: 5166

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5826 AN: 10574

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.521 AC: 35398 AN: 67980

Other (OTH) AF: 0.524 AC: 1108 AN: 2116

Alfa AF: 0.520 Hom.: 88315

Bravo AF: 0.515

Asia WGS AF: 0.464 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.75
PhyloP100		-0.82
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: rs1369450; hg19: chr8-131892722;