rs263232

Positions:

• chr8-130795923-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001115.3(ADCY8):​c.3060+4503G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 152,252 control chromosomes in the GnomAD database, including 471 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 0.066 (471 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.3060+4503G>T		intron_variant		ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4	c.2970+4503G>T		intron_variant			XP_005250826.1
ADCY8	XM_006716501.4	c.2862+4503G>T		intron_variant			XP_006716564.1
ADCY8	XM_017013006.2	c.2772+4503G>T		intron_variant			XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.3060+4503G>T		intron_variant		1	NM_001115.3	ENSP00000286355	P1
ADCY8	ENST00000377928.7	c.2667+4503G>T		intron_variant		1		ENSP00000367161

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10120 AN: 152134 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0665 AC: 10118 AN: 152252 Hom.: 471 Cov.: 32 AF XY: 0.0658 AC XY: 4900 AN XY: 74432

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0853 Hom.: 852

Bravo AF: 0.0614

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs263232; hg19: chr8-131808169;