Variant 16-19871996-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016235.3(GPRC5B):c.850G>A(p.Val284Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

GPRC5B
NM_016235.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

Variant links:

Genes affected

GPRC5B (HGNC:13308): (G protein-coupled receptor class C group 5 member B) This gene encodes a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The encoded protein may modulate insulin secretion and increased protein expression is associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

GPRC5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033668786).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	2/4	ENST00000300571.7	NP_057319.1	Q9NZH0-1A0A024QYX2
GPRC5B	NM_001304771.1 linkuse as main transcript	c.1243G>A	p.Val415Ile	missense_variant	2/4		NP_001291700.1	B7Z831

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPRC5B	ENST00000300571.7 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	2/4	1	NM_016235.3	ENSP00000300571.2	Q9NZH0-1
GPRC5B	ENST00000535671.5 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	1/3	1		ENSP00000442858.1	Q9NZH0-2
GPRC5B	ENST00000569479.5 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	2/4	5		ENSP00000454727.1	Q9NZH0-1
GPRC5B	ENST00000569847.1 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	2/4	2		ENSP00000457283.1	Q9NZH0-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251168

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000800

AC:

117

AN:

1461830

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000872

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.850G>A (p.V284I) alteration is located in exon 2 (coding exon 1) of the GPRC5B gene. This alteration results from a G to A substitution at nucleotide position 850, causing the valine (V) at amino acid position 284 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;.;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.75

.;T;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.040

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.39

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.44

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0090

B;.;B;B

Vest4

0.21

MVP

0.18

MPC

0.34

ClinPred

0.015

GERP RS

2.1

Varity_R

0.020

gMVP

0.48

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