19-45678134-G-C

Variant names:

• chr19-45678134-G-C
• rs1800437
• NM_000164.4:c.1060G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000590918.6(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.

• Frequency:
  • Genomes: 𝑓 0.17 (2479 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28035 hom.)
• Consequence: GIPR ENST00000590918.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 117 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590918.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPR	NM_000164.4	MANE Select	c.1060G>C	p.Glu354Gln	missense	Exon 12 of 14	NP_000155.1
	GIPR	NM_001308418.2		c.952G>C	p.Glu318Gln	missense	Exon 11 of 13	NP_001295347.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPR	ENST00000590918.6	TSL:1 MANE Select	c.1060G>C	p.Glu354Gln	missense	Exon 12 of 14	ENSP00000467494.1
	GIPR	ENST00000304207.12	TSL:1	c.952G>C	p.Glu318Gln	missense	Exon 11 of 13	ENSP00000305321.8
	GIPR	ENST00000263281.7	TSL:1	c.1060G>C	p.Glu354Gln	missense	Exon 12 of 13	ENSP00000263281.3

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

GnomAD2 exomes AF: 0.182 AC: 44732 AN: 245834 AF XY: 0.184

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 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

African (AFR) AF: 0.111 AC: 3725 AN: 33432

American (AMR) AF: 0.102 AC: 4545 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7361 AN: 26088

East Asian (EAS) AF: 0.215 AC: 8529 AN: 39598

South Asian (SAS) AF: 0.144 AC: 12397 AN: 86084

European-Finnish (FIN) AF: 0.242 AC: 12767 AN: 52772

Middle Eastern (MID) AF: 0.184 AC: 971 AN: 5266

European-Non Finnish (NFE) AF: 0.198 AC: 219443 AN: 1111052

Other (OTH) AF: 0.189 AC: 11369 AN: 60224

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

African (AFR) AF: 0.115 AC: 4770 AN: 41492

American (AMR) AF: 0.132 AC: 2018 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1021 AN: 5142

South Asian (SAS) AF: 0.151 AC: 726 AN: 4818

European-Finnish (FIN) AF: 0.228 AC: 2405 AN: 10570

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14004 AN: 67974

Other (OTH) AF: 0.198 AC: 417 AN: 2110

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 v4.9

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
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.15
MPC		0.88
ClinPred		0.023	T
GERP RS		3.1
Varity_R		0.61
gMVP		0.57
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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