Variant chr14-91234181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001177676.2(GPR68):c.870C>T(p.Ser290=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,548,510 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 11 hom. )

Consequence

GPR68
NM_001177676.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.962

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-91234181-G-A is Benign according to our data. Variant chr14-91234181-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038180.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.962 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR68	NM_001177676.2 linkuse as main transcript	c.870C>T	p.Ser290=	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.870C>T	p.Ser290=	synonymous_variant	2/2		NM_001177676.2	ENSP00000498702	P1
GPR68	ENST00000531499.2 linkuse as main transcript	c.870C>T	p.Ser290=	synonymous_variant	2/2	1		ENSP00000434045	P1
GPR68	ENST00000535815.5 linkuse as main transcript	c.870C>T	p.Ser290=	synonymous_variant	2/2	1		ENSP00000440797	P1
GPR68	ENST00000529102.1 linkuse as main transcript	c.870C>T	p.Ser290=	synonymous_variant	2/2	1		ENSP00000432740

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00141

AC:

219

AN:

155612

Hom.:

AF XY:

0.00126

AC XY:

105

AN XY:

83442

show subpopulations

Gnomad AFR exome

AF:

0.000772

Gnomad AMR exome

AF:

0.0000789

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00123

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00227

AC:

3176

AN:

1396134

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1492

AN XY:

689758

show subpopulations

Gnomad4 AFR exome

AF:

0.000470

Gnomad4 AMR exome

AF:

0.0000825

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152376

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00159

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPR68-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 09, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.84

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