Variant NM_005314.3:c.658G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005314.3(GRPR):c.658G>A(p.Val220Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,192,711 control chromosomes in the GnomAD database, including 1 homozygotes. There are 58 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., 27 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 31 hem. )

Consequence

GRPR
NM_005314.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.458

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067535937).

BP6

Variant X-16150549-G-A is Benign according to our data. Variant chrX-16150549-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 780684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPR	NM_005314.3 link	c.658G>A	p.Val220Ile	missense_variant	Exon 2 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.658G>A	p.Val220Ile	missense_variant	Exon 2 of 3	1	NM_005314.3	ENSP00000369643.2		P30550

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

113

AN:

111519

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

AN XY:

33713

show subpopulations

Gnomad AFR

AF:

0.00356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.000351

AC:

AN:

182440

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

67340

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.000292

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:

0.0000865

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000105

AC:

114

AN:

1081139

Hom.:

Cov.:

AF XY:

0.0000893

AC XY:

AN XY:

347327

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.000369

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000286

GnomAD4 genome

AF:

0.00101

AC:

113

AN:

111572

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

AN XY:

33776

show subpopulations

Gnomad4 AFR

AF:

0.00355

Gnomad4 AMR

AF:

0.000286

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000657

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000873

ESP6500AA

AF:

0.00339

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.67

DANN

Benign

0.76

DEOGEN2

Benign

0.085

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.52

M_CAP

Benign

0.020

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.12

PrimateAI

Benign

0.26

PROVEAN

Benign

0.12

REVEL

Benign

0.090

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.087

MVP

0.47

MPC

0.28

ClinPred

0.00042

GERP RS

-0.096

Varity_R

0.037

gMVP

0.13

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