rs2302382

Positions:

• chr19-45669311-C-A
• chr19-45669311-C-G

Variant summary

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

The NM_000164.4(GIPR):​c.-44-166C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,206 control chromosomes in the GnomAD database, including 2,669 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 0.18 (2669 hom., cov: 31)
• Consequence: GIPR NM_000164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPR	NM_000164.4	c.-44-166C>A		intron_variant		ENST00000590918.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPR	ENST00000590918.6	c.-44-166C>A		intron_variant		1	NM_000164.4	P2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26828 AN: 152088 Hom.: 2672 Cov.: 31

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26819 AN: 152206 Hom.: 2669 Cov.: 31 AF XY: 0.176 AC XY: 13121 AN XY: 74416

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.184

Alfa AF: 0.158 Hom.: 468

Bravo AF: 0.171

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.82
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 4

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302382; hg19: chr19-46172569; COSMIC: COSV54426607; COSMIC: COSV54426607;