Variant 14-91234502-G-A 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_001177676.2(GPR68):c.549C>T(p.Arg183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,830 control chromosomes in the GnomAD database, including 4,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 1813 hom., cov: 32)

Exomes 𝑓: 0.023 ( 2487 hom. )

Consequence

GPR68
NM_001177676.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

Variant links:

Genes affected

GPR68 (HGNC:4519): (G protein-coupled receptor 68) The protein encoded by this gene is a G protein-coupled receptor for sphingosylphosphorylcholine. The encoded protein is a proton-sensing receptor, inactive at pH 7.8 but active at pH 6.8. Mutations in this gene are a cause of amelogenesis imperfecta. [provided by RefSeq, Feb 2017]

GPR68 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-91234502-G-A is Benign according to our data. Variant chr14-91234502-G-A is described in ClinVar as [Benign]. Clinvar id is 1286992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2 linkuse as main transcript	c.549C>T	p.Arg183=	synonymous_variant	2/2	ENST00000650645.1	NP_001171147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GPR68	ENST00000650645.1 linkuse as main transcript	c.549C>T	p.Arg183=	synonymous_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2 linkuse as main transcript	c.549C>T	p.Arg183=	synonymous_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5 linkuse as main transcript	c.549C>T	p.Arg183=	synonymous_variant	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1 linkuse as main transcript	c.549C>T	p.Arg183=	synonymous_variant	2/2	1		ENSP00000432740

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14633

AN:

152140

Hom.:

1805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0372

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.00744

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.0779

GnomAD3 exomes

AF:

0.0520

AC:

12982

AN:

249654

Hom.:

1139

AF XY:

0.0487

AC XY:

6584

AN XY:

135172

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0547

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.0912

Gnomad FIN exome

AF:

0.00743

Gnomad NFE exome

AF:

0.00680

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0234

AC:

34238

AN:

1461570

Hom.:

2487

Cov.:

AF XY:

0.0245

AC XY:

17849

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.0204

Gnomad4 ASJ exome

AF:

0.0521

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.00874

Gnomad4 NFE exome

AF:

0.00525

Gnomad4 OTH exome

AF:

0.0444

GnomAD4 genome

AF:

0.0963

AC:

14670

AN:

152260

Hom.:

1813

Cov.:

AF XY:

0.0953

AC XY:

7097

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.00744

Gnomad4 NFE

AF:

0.00656

Gnomad4 OTH

AF:

0.0784

Alfa

AF:

0.0303

Hom.:

537

Bravo

AF:

0.107

Asia WGS

AF:

0.147

AC:

511

AN:

3478

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	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.55

DANN

Benign

0.39

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