chr19-45679046-T-A

Variant names:

• chr19-45679046-T-A
• rs10423928
• NM_000164.4:c.1152+820T>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.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
• Publications: 124 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 (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000164.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPR	NM_000164.4	MANE Select	c.1152+820T>A		intron	N/A	NP_000155.1
	GIPR	NM_001308418.2		c.1044+820T>A		intron	N/A	NP_001295347.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPR	ENST00000590918.6	TSL:1 MANE Select	c.1152+820T>A		intron	N/A	ENSP00000467494.1
	GIPR	ENST00000304207.12	TSL:1	c.1044+820T>A		intron	N/A	ENSP00000305321.8
	GIPR	ENST00000263281.7	TSL:1	c.1152+820T>A		intron	N/A	ENSP00000263281.3

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

African (AFR) AF: 0.153 AC: 6343 AN: 41528

American (AMR) AF: 0.135 AC: 2064 AN: 15286

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

East Asian (EAS) AF: 0.199 AC: 1032 AN: 5184

South Asian (SAS) AF: 0.150 AC: 726 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2402 AN: 10584

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14023 AN: 68010

Other (OTH) AF: 0.203 AC: 427 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		-0.33
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: rs10423928; hg19: chr19-46182304;