Variant 8-130800510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.951

Variant links:

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]

ADCY8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCY8	NM_001115.3 linkuse as main transcript	c.2976G>A	p.Ala992=	synonymous_variant	15/18	ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4 linkuse as main transcript	c.2886G>A	p.Ala962=	synonymous_variant	14/17		XP_005250826.1
ADCY8	XM_006716501.4 linkuse as main transcript	c.2778G>A	p.Ala926=	synonymous_variant	14/17		XP_006716564.1
ADCY8	XM_017013006.2 linkuse as main transcript	c.2688G>A	p.Ala896=	synonymous_variant	13/16		XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10 linkuse as main transcript	c.2976G>A	p.Ala992=	synonymous_variant	15/18	1	NM_001115.3	ENSP00000286355	P1
ADCY8	ENST00000377928.7 linkuse as main transcript	c.2583G>A	p.Ala861=	synonymous_variant	12/15	1		ENSP00000367161

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3490

AN:

152056

Hom.:

132

Cov.:

show subpopulations

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.:

AF XY:

0.00454

AC XY:

617

AN XY:

135902

show subpopulations

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.:

AF XY:

0.00212

AC XY:

1539

AN XY:

727234

show subpopulations

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.:

AF XY:

0.0225

AC XY:

1676

AN XY:

74408

show subpopulations

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.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over