chr19-45676926-C-T

Position:

• chr19-45676926-C-T

Variant summary

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

The NM_000164.4(GIPR):​c.634-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,610,690 control chromosomes in the GnomAD database, including 30,607 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.17 (2480 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28127 hom.)
• Consequence: GIPR NM_000164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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.634-23C>T		intron_variant		ENST00000590918.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPR	ENST00000590918.6	c.634-23C>T		intron_variant		1	NM_000164.4	P2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26439 AN: 152112 Hom.: 2484 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.183 AC: 45631 AN: 248690 Hom.: 4471 AF XY: 0.185 AC XY: 24976 AN XY: 134750

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0973

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.192 AC: 280654 AN: 1458460 Hom.: 28127 Cov.: 35 AF XY: 0.192 AC XY: 139266 AN XY: 725726

Gnomad4 AFR exome AF: 0.107

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: 0.243

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.174 AC: 26442 AN: 152230 Hom.: 2480 Cov.: 32 AF XY: 0.173 AC XY: 12867 AN XY: 74436

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.198

Alfa AF: 0.200 Hom.: 4325

Bravo AF: 0.164

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.3
DANN	Benign	0.72
BranchPoint Hunter		1.0

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: rs11672660; hg19: chr19-46180184; COSMIC: COSV54423233; COSMIC: COSV54423233;