chr19-45678134-G-C

Position:

• chr19-45678134-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000164.4(GIPR):​c.1060G>C​(p.Glu354Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,060 control chromosomes in the GnomAD database, including 30,514 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2479 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28035 hom.)
• Consequence: GIPR NM_000164.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPR	NM_000164.4	c.1060G>C	p.Glu354Gln	missense_variant	12/14	ENST00000590918.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPR	ENST00000590918.6	c.1060G>C	p.Glu354Gln	missense_variant	12/14	1	NM_000164.4	P2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26534 AN: 151948 Hom.: 2483 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.197

GnomAD3 exomes AF: 0.182 AC: 44732 AN: 245834 Hom.: 4273 AF XY: 0.184 AC XY: 24509 AN XY: 133338

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0970

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.193 AC: 281107 AN: 1458994 Hom.: 28035 Cov.: 37 AF XY: 0.192 AC XY: 139375 AN XY: 725728

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.175 AC: 26536 AN: 152066 Hom.: 2479 Cov.: 32 AF XY: 0.173 AC XY: 12886 AN XY: 74340

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.198

Alfa AF: 0.204 Hom.: 2519

Bravo AF: 0.165

TwinsUK AF: 0.200 AC: 741

ALSPAC AF: 0.196 AC: 754

ESP6500AA AF: 0.113 AC: 500

ESP6500EA AF: 0.203 AC: 1750

ExAC AF: 0.183 AC: 22260

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;.
MutationTaster	Benign	0.021	P;P;P
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	.;N;D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	.;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.15
MPC		0.88
ClinPred		0.023	T
GERP RS		3.1
Varity_R		0.61
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.43		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800437; hg19: chr19-46181392; COSMIC: COSV54422837; COSMIC: COSV54422837;