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. The variant received -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
• Publications: 12 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	NM_001115.3	MANE Select	c.979C>T	p.Leu327Leu	synonymous	Exon 2 of 18	NP_001106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	ENST00000286355.10	TSL:1 MANE Select	c.979C>T	p.Leu327Leu	synonymous	Exon 2 of 18	ENSP00000286355.5
	ADCY8	ENST00000377928.7	TSL:1	c.979C>T	p.Leu327Leu	synonymous	Exon 2 of 15	ENSP00000367161.3
	ADCY8	ENST00000522949.1	TSL:5	c.-131C>T		5_prime_UTR	Exon 2 of 7	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

GnomAD2 exomes AF: 0.206 AC: 51806 AN: 250888 AF XY: 0.201

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 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

African (AFR) AF: 0.643 AC: 21501 AN: 33456

American (AMR) AF: 0.223 AC: 9984 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4825 AN: 26130

East Asian (EAS) AF: 0.0734 AC: 2914 AN: 39694

South Asian (SAS) AF: 0.245 AC: 21135 AN: 86226

European-Finnish (FIN) AF: 0.139 AC: 7409 AN: 53416

Middle Eastern (MID) AF: 0.260 AC: 1497 AN: 5748

European-Non Finnish (NFE) AF: 0.161 AC: 178534 AN: 1111448

Other (OTH) AF: 0.200 AC: 12052 AN: 60350

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

African (AFR) AF: 0.630 AC: 26151 AN: 41520

American (AMR) AF: 0.227 AC: 3475 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3472

East Asian (EAS) AF: 0.0805 AC: 418 AN: 5190

South Asian (SAS) AF: 0.228 AC: 1101 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10594

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11075 AN: 68008

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.206 Hom.: 5869

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		0.96
PromoterAI		-0.0025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2228950; hg19: chr8-132002770; COSMIC: COSV53910159;