rs263249

Variant names:

• chr8-130783014-A-G
• rs263249
• NM_001115.3:c.3268+677T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-130783014-A-G
• chr8-130783014-A-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.3268+677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,070 control chromosomes in the GnomAD database, including 35,555 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 0.67 (35555 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.3268+677T>C		intron_variant	Intron 17 of 17	ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4	c.3178+677T>C		intron_variant	Intron 16 of 16		XP_005250826.1
ADCY8	XM_006716501.4	c.3070+677T>C		intron_variant	Intron 16 of 16		XP_006716564.1
ADCY8	XM_017013006.2	c.2980+677T>C		intron_variant	Intron 15 of 15		XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.3268+677T>C		intron_variant	Intron 17 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.2875+677T>C		intron_variant	Intron 14 of 14	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102366 AN: 151952 Hom.: 35534 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.674 AC: 102437 AN: 152070 Hom.: 35555 Cov.: 32 AF XY: 0.659 AC XY: 48937 AN XY: 74308

African (AFR) AF: 0.811 AC: 33644 AN: 41482

American (AMR) AF: 0.614 AC: 9374 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2450 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1703 AN: 5172

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5466 AN: 10546

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45468 AN: 67992

Other (OTH) AF: 0.658 AC: 1389 AN: 2112

Alfa AF: 0.706 Hom.: 6229

Bravo AF: 0.686

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		-0.58
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: rs263249; hg19: chr8-131795260;