Variant X-16124349-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005314.3(GRPR):c.396G>A(p.Thr132Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,207,653 control chromosomes in the GnomAD database, including 65 homozygotes. There are 4,499 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 3 hom., 228 hem., cov: 23)

Exomes 𝑓: 0.012 ( 62 hom. 4271 hem. )

Consequence

GRPR
NM_005314.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.77

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-16124349-G-A is Benign according to our data. Variant chrX-16124349-G-A is described in ClinVar as [Benign]. Clinvar id is 790473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-16124349-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.77 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPR	NM_005314.3 link	c.396G>A	p.Thr132Thr	synonymous_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.396G>A	p.Thr132Thr	synonymous_variant	Exon 1 of 3	1	NM_005314.3	ENSP00000369643.2		P30550

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

828

AN:

111127

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

228

AN XY:

33325

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00191

Gnomad ASJ

AF:

0.00644

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00828

AC:

1511

AN:

182501

Hom.:

AF XY:

0.00816

AC XY:

548

AN XY:

67179

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00430

Gnomad FIN exome

AF:

0.00898

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.00730

GnomAD4 exome

AF:

0.0118

AC:

12990

AN:

1096474

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

4271

AN XY:

361890

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00588

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00492

Gnomad4 FIN exome

AF:

0.00874

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.00875

GnomAD4 genome

AF:

0.00745

AC:

828

AN:

111179

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

228

AN XY:

33387

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00191

Gnomad4 ASJ

AF:

0.00644

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00459

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00664

EpiCase

AF:

0.0112

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

GRPR-related disorder

Benign:1

Aug 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

-0.86

CADD

Benign

1.0

DANN

Benign

0.58

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