8-130800510-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001115.3(ADCY8):c.2976G>A(p.Ala992=) 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, single submitter B:1
• Conservation: PhyloP100: -0.951

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 -15 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 id is 785263.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY8	NM_001115.3	c.2976G>A	p.Ala992=	synonymous_variant	15/18	ENST00000286355.10
ADCY8	XM_005250769.4	c.2886G>A	p.Ala962=	synonymous_variant	14/17
ADCY8	XM_006716501.4	c.2778G>A	p.Ala926=	synonymous_variant	14/17
ADCY8	XM_017013006.2	c.2688G>A	p.Ala896=	synonymous_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY8	ENST00000286355.10	c.2976G>A	p.Ala992=	synonymous_variant	15/18	1	NM_001115.3	P1
ADCY8	ENST00000377928.7	c.2583G>A	p.Ala861=	synonymous_variant	12/15	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

GnomAD3 exomes AF: 0.00573 AC: 1441 AN: 251454 Hom.: 51 AF XY: 0.00454 AC XY: 617 AN XY: 135902

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 SAS exome AF: 0.0000980

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

Gnomad4 AFR exome AF: 0.0802

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000174

Gnomad4 OTH exome AF: 0.00593

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

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0120 Hom.: 29

Bravo AF: 0.0267

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.9
Dann	Benign	0.30

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: rs62640023; hg19: chr8-131812756;