17-48961770-T-C

Variant names:

• chr17-48961770-T-C
• rs2291725
• NM_004123.3:c.307A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004123.3(GIP):​c.307A>G​(p.Ser103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,610,816 control chromosomes in the GnomAD database, including 213,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (15132 hom., cov: 31)
  • Exomes 𝑓: 0.52 (198804 hom.)
• Consequence: GIP NM_004123.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 85 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.907024E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIP	NM_004123.3	c.307A>G	p.Ser103Gly	missense_variant	Exon 4 of 6	ENST00000357424.2	NP_004114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIP	ENST00000357424.2	c.307A>G	p.Ser103Gly	missense_variant	Exon 4 of 6	1	NM_004123.3	ENSP00000350005.2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62177 AN: 151920 Hom.: 15139 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.436

GnomAD2 exomes AF: 0.496 AC: 123525 AN: 249106 AF XY: 0.505

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.705

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.526

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.516 AC: 752581 AN: 1458778 Hom.: 198804 Cov.: 37 AF XY: 0.517 AC XY: 375515 AN XY: 725890

African (AFR) AF: 0.116 AC: 3895 AN: 33466

American (AMR) AF: 0.435 AC: 19426 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13711 AN: 26106

East Asian (EAS) AF: 0.718 AC: 28495 AN: 39678

South Asian (SAS) AF: 0.491 AC: 42355 AN: 86194

European-Finnish (FIN) AF: 0.516 AC: 27030 AN: 52346

Middle Eastern (MID) AF: 0.470 AC: 2708 AN: 5764

European-Non Finnish (NFE) AF: 0.527 AC: 585344 AN: 1110280

Other (OTH) AF: 0.491 AC: 29617 AN: 60314

GnomAD4 genome AF: 0.409 AC: 62164 AN: 152038 Hom.: 15132 Cov.: 31 AF XY: 0.411 AC XY: 30544 AN XY: 74298

African (AFR) AF: 0.135 AC: 5622 AN: 41512

American (AMR) AF: 0.412 AC: 6285 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3637 AN: 5150

South Asian (SAS) AF: 0.506 AC: 2442 AN: 4830

European-Finnish (FIN) AF: 0.516 AC: 5440 AN: 10552

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35346 AN: 67958

Other (OTH) AF: 0.440 AC: 930 AN: 2114

Alfa AF: 0.491 Hom.: 59808

Bravo AF: 0.393

TwinsUK AF: 0.522 AC: 1937

ALSPAC AF: 0.510 AC: 1967

ESP6500AA AF: 0.143 AC: 628

ESP6500EA AF: 0.535 AC: 4604

ExAC AF: 0.490 AC: 59534

Asia WGS AF: 0.547 AC: 1898 AN: 3476

EpiCase AF: 0.523

EpiControl AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.34
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0000019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.12	N
PhyloP100		0.050
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.027
Sift	Benign	0.77	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.0020
MPC		0.022
ClinPred		0.0052	T
GERP RS		-5.1
Varity_R		0.035
gMVP		0.039
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291725; hg19: chr17-47039132; COSMIC: COSV62467017;