chr17-48960949-C-T

Variant summary

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

The NM_004123.3(GIP):​c.389G>A​(p.Arg130Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,609,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

GIP
NM_004123.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.243
Variant links:
Genes affected
GIP (HGNC:4270): (gastric inhibitory polypeptide) This gene encodes an incretin hormone and belongs to the glucagon superfamily. The encoded protein is important in maintaining glucose homeostasis as it is a potent stimulator of insulin secretion from pancreatic beta-cells following food ingestion and nutrient absorption. This gene stimulates insulin secretion via its G protein-coupled receptor activation of adenylyl cyclase and other signal transduction pathways. It is a relatively poor inhibitor of gastric acid secretion. [provided by RefSeq, Jul 2008]

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=0.039033085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GIPNM_004123.3 linkc.389G>A p.Arg130Gln missense_variant Exon 5 of 6 ENST00000357424.2 NP_004114.1 P09681

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GIPENST00000357424.2 linkc.389G>A p.Arg130Gln missense_variant Exon 5 of 6 1 NM_004123.3 ENSP00000350005.2 P09681

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152126
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000574
AC:
14
AN:
243758
Hom.:
0
AF XY:
0.0000837
AC XY:
11
AN XY:
131456
show subpopulations
Gnomad AFR exome
AF:
0.0000649
Gnomad AMR exome
AF:
0.0000296
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000689
Gnomad FIN exome
AF:
0.0000954
Gnomad NFE exome
AF:
0.0000723
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000418
AC:
61
AN:
1457664
Hom.:
0
Cov.:
30
AF XY:
0.0000414
AC XY:
30
AN XY:
724520
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000453
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000471
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152244
Hom.:
0
Cov.:
31
AF XY:
0.0000537
AC XY:
4
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.389G>A (p.R130Q) alteration is located in exon 5 (coding exon 4) of the GIP gene. This alteration results from a G to A substitution at nucleotide position 389, causing the arginine (R) at amino acid position 130 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.80
N
REVEL
Benign
0.021
Sift
Benign
0.13
T
Sift4G
Uncertain
0.043
D
Polyphen
0.066
B
Vest4
0.13
MutPred
0.22
Gain of relative solvent accessibility (P = 0.2629);
MVP
0.23
MPC
0.036
ClinPred
0.049
T
GERP RS
0.68
Varity_R
0.048
gMVP
0.061

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.

Other links and lift over

dbSNP: rs148732781; hg19: chr17-47038311; API