chr8-131015569-G-C

Variant names:

• chr8-131015569-G-C
• rs928136
• NM_001115.3:c.960+23805C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001115.3(ADCY8):​c.960+23805C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 152,192 control chromosomes in the GnomAD database, including 57 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 0.026 (57 hom., cov: 32)
• Consequence: ADCY8 NM_001115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• 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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0255 (3884/152192) while in subpopulation NFE AF = 0.0397 (2699/67970). AF 95% confidence interval is 0.0385. There are 57 homozygotes in GnomAd4. There are 1862 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.960+23805C>G		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.960+23805C>G		intron_variant	Intron 1 of 17	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.960+23805C>G		intron_variant	Intron 1 of 14	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3884 AN: 152074 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00686

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0255 AC: 3884 AN: 152192 Hom.: 57 Cov.: 32 AF XY: 0.0250 AC XY: 1862 AN XY: 74404

African (AFR) AF: 0.00684 AC: 284 AN: 41550

American (AMR) AF: 0.0109 AC: 166 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4826

European-Finnish (FIN) AF: 0.0397 AC: 420 AN: 10580

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2699 AN: 67970

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0164 Hom.: 8

Bravo AF: 0.0214

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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: rs928136; hg19: chr8-132027815;