NM_005314.3:c.17G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005314.3(GRPR):c.17G>C(p.Cys6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,207,272 control chromosomes in the GnomAD database, including 2 homozygotes. There are 311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., 21 hem., cov: 23)

Exomes 𝑓: 0.00068 ( 2 hom. 290 hem. )

Consequence

GRPR
NM_005314.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

GRPR (HGNC:4609): (gastrin releasing peptide receptor) Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene. [provided by RefSeq, Jul 2008]

GRPR 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 (MetaRNN=0.00465551).

BP6

Variant X-16123970-G-C is Benign according to our data. Variant chrX-16123970-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 721453.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPR	NM_005314.3 link	c.17G>C	p.Cys6Ser	missense_variant	Exon 1 of 3	ENST00000380289.3	NP_005305.1	P30550X5D7H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRPR	ENST00000380289.3 link	c.17G>C	p.Cys6Ser	missense_variant	Exon 1 of 3	1	NM_005314.3	ENSP00000369643.2		P30550

Frequencies

GnomAD3 genomes

AF:

0.000680

AC:

AN:

111822

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

AN XY:

33996

show subpopulations

Gnomad AFR

AF:

0.0000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000882

AC:

161

AN:

182591

Hom.:

AF XY:

0.00121

AC XY:

AN XY:

67163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.000936

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000677

AC:

742

AN:

1095397

Hom.:

Cov.:

AF XY:

0.000804

AC XY:

290

AN XY:

360907

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.000826

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.0000996

Gnomad4 NFE exome

AF:

0.000642

Gnomad4 OTH exome

AF:

0.000717

GnomAD4 genome

AF:

0.000670

AC:

AN:

111875

Hom.:

Cov.:

AF XY:

0.000617

AC XY:

AN XY:

34059

show subpopulations

Gnomad4 AFR

AF:

0.0000650

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00114

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00338

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000727

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.00103

AC:

125

EpiCase

AF:

0.00267

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GRPR-related disorder

Benign:1

Apr 20, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.076

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.30

PROVEAN

Benign

0.56

REVEL

Benign

0.090

Sift

Benign

0.15

Sift4G

Benign

0.84

Polyphen

0.035

Vest4

0.034

MutPred

0.42

Gain of disorder (P = 0.0012);

MVP

0.85

MPC

0.42

ClinPred

0.018

GERP RS

4.7

Varity_R

0.29

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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