chr19-45669020-G-A

Variant names:

• chr19-45669020-G-A
• rs11671664
• NM_000164.4:c.-44-457G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000164.4(GIPR):​c.-44-457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,074 control chromosomes in the GnomAD database, including 1,366 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 0.12 (1366 hom., cov: 33)
• Consequence: GIPR NM_000164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 65 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: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPR	NM_000164.4	c.-44-457G>A		intron_variant	Intron 1 of 13	ENST00000590918.6	NP_000155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPR	ENST00000590918.6	c.-44-457G>A		intron_variant	Intron 1 of 13	1	NM_000164.4	ENSP00000467494.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18121 AN: 151956 Hom.: 1367 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.119 AC: 18131 AN: 152074 Hom.: 1366 Cov.: 33 AF XY: 0.122 AC XY: 9069 AN XY: 74342

African (AFR) AF: 0.115 AC: 4788 AN: 41492

American (AMR) AF: 0.0897 AC: 1370 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2180 AN: 5140

South Asian (SAS) AF: 0.112 AC: 540 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1183 AN: 10592

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7197 AN: 67976

Other (OTH) AF: 0.143 AC: 301 AN: 2110

Alfa AF: 0.115 Hom.: 5428

Bravo AF: 0.122

Asia WGS AF: 0.227 AC: 792 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	7.4
DANN	Benign	0.70
PhyloP100		0.36
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: rs11671664; hg19: chr19-46172278;