chr8-130800510-C-T

Variant names:

• chr8-130800510-C-T
• rs62640023
• NM_001115.3:c.2976G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001115.3(ADCY8):​c.2976G>A​(p.Ala992Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,614,040 control chromosomes in the GnomAD database, including 246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (134 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (112 hom.)
• Consequence: ADCY8 NM_001115.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.951
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-130800510-C-T is Benign according to our data. Variant chr8-130800510-C-T is described in ClinVar as Benign. ClinVar VariationId is 785263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.951 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	NM_001115.3	MANE Select	c.2976G>A	p.Ala992Ala	synonymous	Exon 15 of 18	NP_001106.1	P40145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY8	ENST00000286355.10	TSL:1 MANE Select	c.2976G>A	p.Ala992Ala	synonymous	Exon 15 of 18	ENSP00000286355.5	P40145
	ADCY8	ENST00000377928.7	TSL:1	c.2583G>A	p.Ala861Ala	synonymous	Exon 12 of 15	ENSP00000367161.3	E7EVL1
	ADCY8	ENST00000912159.1		c.2886G>A	p.Ala962Ala	synonymous	Exon 14 of 17	ENSP00000582218.1

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3490 AN: 152056 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00573 AC: 1441 AN: 251454 AF XY: 0.00454

Gnomad AFR exome AF: 0.0768

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00241 AC: 3527 AN: 1461866 Hom.: 112 Cov.: 33 AF XY: 0.00212 AC XY: 1539 AN XY: 727234

African (AFR) AF: 0.0802 AC: 2685 AN: 33480

American (AMR) AF: 0.00470 AC: 210 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.000174 AC: 193 AN: 1111990

Other (OTH) AF: 0.00593 AC: 358 AN: 60394

GnomAD4 genome AF: 0.0230 AC: 3495 AN: 152174 Hom.: 134 Cov.: 33 AF XY: 0.0225 AC XY: 1676 AN XY: 74408

African (AFR) AF: 0.0786 AC: 3262 AN: 41490

American (AMR) AF: 0.0112 AC: 171 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68008

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.0111 Hom.: 37

Bravo AF: 0.0267

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.30
PhyloP100		-0.95
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: rs62640023; hg19: chr8-131812756; COSMIC: COSV106398496;