chr19-45676926-C-T

Variant names:

• chr19-45676926-C-T
• rs11672660
• NM_000164.4:c.634-23C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 66 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 -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
GIPR	NM_000164.4	c.634-23C>T		intron_variant	Intron 7 of 13	ENST00000590918.6	NP_000155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPR	ENST00000590918.6	c.634-23C>T		intron_variant	Intron 7 of 13	1	NM_000164.4	ENSP00000467494.1

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

GnomAD2 exomes AF: 0.183 AC: 45631 AN: 248690 AF XY: 0.185

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 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

African (AFR) AF: 0.107 AC: 3592 AN: 33438

American (AMR) AF: 0.102 AC: 4581 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7371 AN: 26116

East Asian (EAS) AF: 0.215 AC: 8544 AN: 39676

South Asian (SAS) AF: 0.144 AC: 12415 AN: 86206

European-Finnish (FIN) AF: 0.243 AC: 12714 AN: 52250

Middle Eastern (MID) AF: 0.187 AC: 1076 AN: 5756

European-Non Finnish (NFE) AF: 0.197 AC: 218987 AN: 1110010

Other (OTH) AF: 0.189 AC: 11374 AN: 60300

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

African (AFR) AF: 0.112 AC: 4655 AN: 41560

American (AMR) AF: 0.131 AC: 2009 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5168

South Asian (SAS) AF: 0.150 AC: 727 AN: 4832

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14004 AN: 67990

Other (OTH) AF: 0.198 AC: 419 AN: 2116

Alfa AF: 0.196 Hom.: 5265

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
PhyloP100		-0.91
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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