rs10423928

Positions:

• chr19-45679046-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000164.4(GIPR):​c.1152+820T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,196 control chromosomes in the GnomAD database, including 2,717 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 0.19 (2717 hom., cov: 32)
• Consequence: GIPR NM_000164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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	Protein	UniProt
GIPR	NM_000164.4	c.1152+820T>A		intron_variant		ENST00000590918.6	NP_000155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPR	ENST00000590918.6	c.1152+820T>A		intron_variant		1	NM_000164.4	ENSP00000467494	P2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28183 AN: 152078 Hom.: 2721 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.185 AC: 28194 AN: 152196 Hom.: 2717 Cov.: 32 AF XY: 0.184 AC XY: 13665 AN XY: 74392

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.203

Alfa AF: 0.199 Hom.: 398

Bravo AF: 0.177

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10423928; hg19: chr19-46182304;