chr19-45669554-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000164.4(GIPR):ā€‹c.34C>Gā€‹(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000049 in 1,429,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000049 ( 0 hom. )

Consequence

GIPR
NM_000164.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.230
Variant links:
Genes affected
GIPR (HGNC:4271): (gastric inhibitory polypeptide receptor) This gene encodes a G-protein coupled receptor for gastric inhibitory polypeptide (GIP), which was originally identified as an activity in gut extracts that inhibited gastric acid secretion and gastrin release, but subsequently was demonstrated to stimulate insulin release in the presence of elevated glucose. Mice lacking this gene exhibit higher blood glucose levels with impaired initial insulin response after oral glucose load. Defect in this gene thus may contribute to the pathogenesis of diabetes. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.100287735).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GIPRNM_000164.4 linkuse as main transcriptc.34C>G p.Arg12Gly missense_variant 2/14 ENST00000590918.6 NP_000155.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GIPRENST00000590918.6 linkuse as main transcriptc.34C>G p.Arg12Gly missense_variant 2/141 NM_000164.4 ENSP00000467494 P2P48546-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000490
AC:
7
AN:
1429818
Hom.:
0
Cov.:
31
AF XY:
0.00000847
AC XY:
6
AN XY:
708636
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000637
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

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 submitterclinical testingAmbry GeneticsSep 25, 2023The c.34C>G (p.R12G) alteration is located in exon 2 (coding exon 1) of the GIPR gene. This alteration results from a C to G substitution at nucleotide position 34, causing the arginine (R) at amino acid position 12 to be replaced by a glycine (G). 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
0.075
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.;.
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.50
T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.3
.;N;N
REVEL
Benign
0.050
Sift
Benign
0.26
.;T;T
Sift4G
Benign
0.20
T;T;T
Polyphen
0.013
B;B;.
Vest4
0.17
MutPred
0.49
Loss of methylation at R12 (P = 0.0587);Loss of methylation at R12 (P = 0.0587);Loss of methylation at R12 (P = 0.0587);
MVP
0.36
MPC
0.95
ClinPred
0.76
D
GERP RS
0.32
Varity_R
0.13
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1975427515; hg19: chr19-46172812; API