8-130780564-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001115.3(ADCY8):c.3582G>A(p.Ala1194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,614,130 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (13 hom.)
• Consequence: ADCY8 NM_001115.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.64

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=-0.5).
• BP6: Variant 8-130780564-C-T is Benign according to our data. Variant chr8-130780564-C-T is described in ClinVar as [Benign]. Clinvar id is 713272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00737 (1122/152274) while in subpopulation AFR AF= 0.0255 (1061/41556). AF 95% confidence interval is 0.0243. There are 14 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY8	NM_001115.3	c.3582G>A	p.Ala1194=	synonymous_variant	18/18	ENST00000286355.10
ADCY8	XM_005250769.4	c.3492G>A	p.Ala1164=	synonymous_variant	17/17
ADCY8	XM_006716501.4	c.3384G>A	p.Ala1128=	synonymous_variant	17/17
ADCY8	XM_017013006.2	c.3294G>A	p.Ala1098=	synonymous_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY8	ENST00000286355.10	c.3582G>A	p.Ala1194=	synonymous_variant	18/18	1	NM_001115.3	P1
ADCY8	ENST00000377928.7	c.3189G>A	p.Ala1063=	synonymous_variant	15/15	1

Frequencies

GnomAD3 genomes AF: 0.00737 AC: 1121 AN: 152156 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00192 AC: 482 AN: 251150 Hom.: 7 AF XY: 0.00148 AC XY: 201 AN XY: 135722

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000768 AC: 1122 AN: 1461856 Hom.: 13 Cov.: 35 AF XY: 0.000679 AC XY: 494 AN XY: 727228

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000638

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00737 AC: 1122 AN: 152274 Hom.: 14 Cov.: 32 AF XY: 0.00708 AC XY: 527 AN XY: 74456

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00419 Hom.: 3

Bravo AF: 0.00833

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

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

Jul 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.058
Dann	Benign	0.59

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: rs139593989; hg19: chr8-131792810;