Variant 4-8581306-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_080819.5(GPR78):c.324G>A(p.Val108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,584,456 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 43 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 33 hom. )

Consequence

GPR78
NM_080819.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.683

Variant links:

Genes affected

GPR78 (HGNC:4528): (G protein-coupled receptor 78) The protein encoded by this gene belongs to the G protein-coupled receptor family, which contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. This is an orphan receptor, which displays significant level of constitutive activity. Association analysis shows preliminary evidence for the involvement of this gene in susceptibility to bipolar affective disorder and schizophrenia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

GPR78 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-8581306-G-A is Benign according to our data. Variant chr4-8581306-G-A is described in ClinVar as [Benign]. Clinvar id is 767949.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.683 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1992/152334) while in subpopulation AFR AF= 0.0453 (1885/41582). AF 95% confidence interval is 0.0436. There are 43 homozygotes in gnomad4. There are 932 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR78	NM_080819.5 linkuse as main transcript	c.324G>A	p.Val108=	synonymous_variant	1/3	ENST00000382487.5
GPR78	NR_045511.3 linkuse as main transcript	n.313+602G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPR78	ENST00000382487.5 linkuse as main transcript	c.324G>A	p.Val108=	synonymous_variant	1/3	1	NM_080819.5	P1
GPR78	ENST00000509216.1 linkuse as main transcript	n.468+602G>A		intron_variant, non_coding_transcript_variant		1
GPR78	ENST00000514302.5 linkuse as main transcript	c.324G>A	p.Val108=	synonymous_variant, NMD_transcript_variant	2/14	2

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1991

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00337

AC:

675

AN:

200410

Hom.:

AF XY:

0.00230

AC XY:

256

AN XY:

111396

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00145

AC:

2080

AN:

1432122

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

850

AN XY:

711274

show subpopulations

Gnomad4 AFR exome

AF:

0.0494

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00301

GnomAD4 genome

AF:

0.0131

AC:

1992

AN:

152334

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

932

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0453

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.6

DANN

Benign

0.67

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