Variant chr18-59220305-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002091.5(GRP):c.40G>T(p.Val14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,505,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GRP
NM_002091.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

GRP (HGNC:4605): (gastrin releasing peptide) This gene encodes a member of the bombesin-like family of gastrin-releasing peptides. The encoded preproprotein is proteolytically processed to generate two peptides, gastrin-releasing peptide and neuromedin-C. These peptides regulate numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation. These peptides are also likely to play a role in human cancers of the lung, colon, stomach, pancreas, breast, and prostate. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

GRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037049502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRP	NM_002091.5 linkuse as main transcript	c.40G>T	p.Val14Phe	missense_variant	1/3	ENST00000256857.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRP	ENST00000256857.7 linkuse as main transcript	c.40G>T	p.Val14Phe	missense_variant	1/3	1	NM_002091.5	A2	P07492-1
GRP	ENST00000420468.6 linkuse as main transcript	c.40G>T	p.Val14Phe	missense_variant	1/3	1		P4	P07492-3
GRP	ENST00000529320.2 linkuse as main transcript	c.40G>T	p.Val14Phe	missense_variant	1/3	1			P07492-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

108058

Hom.:

AF XY:

0.0000503

AC XY:

AN XY:

59654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000998

Gnomad OTH exome

AF:

0.000305

GnomAD4 exome

AF:

0.000112

AC:

151

AN:

1353590

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

667468

show subpopulations

Gnomad4 AFR exome

AF:

0.000106

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000124

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000683

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000241

AC:

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

Jan 24, 2024

The c.40G>T (p.V14F) alteration is located in exon 1 (coding exon 1) of the GRP gene. This alteration results from a G to T substitution at nucleotide position 40, causing the valine (V) at amino acid position 14 to be replaced by a phenylalanine (F). 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

0.22

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.26

Sift

Benign

0.099

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

1.0

D;P;D

Vest4

0.56

MutPred

0.67

Loss of stability (P = 0.0467);Loss of stability (P = 0.0467);Loss of stability (P = 0.0467);

MVP

0.72

MPC

0.83

ClinPred

0.74

GERP RS

3.1

Varity_R

0.42

gMVP

0.44

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