rs2228950

Variant names:

• chr8-130990524-G-A
• rs2228950
• NM_001115.3:c.979C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-130990524-G-A
• chr8-130990524-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001115.3(ADCY8):​c.979C>T​(p.Leu327Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,390 control chromosomes in the GnomAD database, including 38,008 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 0.30 (9961 hom., cov: 33)
  • Exomes 𝑓: 0.18 (28047 hom.)
• Consequence: ADCY8 NM_001115.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.958 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.979C>T	p.Leu327Leu	synonymous_variant	Exon 2 of 18	ENST00000286355.10	NP_001106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.979C>T	p.Leu327Leu	synonymous_variant	Exon 2 of 18	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.979C>T	p.Leu327Leu	synonymous_variant	Exon 2 of 15	1		ENSP00000367161.3
ADCY8	ENST00000522949.1	c.-131C>T		5_prime_UTR_variant	Exon 2 of 7	5		ENSP00000428010.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44895 AN: 152098 Hom.: 9932 Cov.: 33

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.274

GnomAD3 exomes AF: 0.206 AC: 51806 AN: 250888 Hom.: 7405 AF XY: 0.201 AC XY: 27292 AN XY: 135542

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.0940

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.178 AC: 259851 AN: 1461174 Hom.: 28047 Cov.: 33 AF XY: 0.179 AC XY: 129987 AN XY: 726926

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0734

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.295 AC: 44963 AN: 152216 Hom.: 9961 Cov.: 33 AF XY: 0.289 AC XY: 21485 AN XY: 74426

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0805

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.271

Alfa AF: 0.186 Hom.: 3450

Bravo AF: 0.317

Asia WGS AF: 0.178 AC: 620 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2228950; hg19: chr8-132002770; COSMIC: COSV53910159;