rs2268641

Variant names:

• chr6-39082490-C-T
• rs2268641
• NM_002062.5:c.1224+1751C>T

Variant summary

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

The NM_002062.5(GLP1R):​c.1224+1751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,942 control chromosomes in the GnomAD database, including 13,006 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 0.41 (13006 hom., cov: 32)
• Consequence: GLP1R NM_002062.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 14 publications found

Genes affected

GLP1R (HGNC:4324): (glucagon like peptide 1 receptor) This gene encodes a 7-transmembrane protein that functions as a receptor for glucagon-like peptide 1 (GLP-1) hormone, which stimulates glucose-induced insulin secretion. This receptor, which functions at the cell surface, becomes internalized in response to GLP-1 and GLP-1 analogs, and it plays an important role in the signaling cascades leading to insulin secretion. It also displays neuroprotective effects in animal models. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type 2 diabetes and stroke. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002062.5. 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
	GLP1R	NM_002062.5	MANE Select	c.1224+1751C>T		intron	N/A	NP_002053.3
	GLP1R	NR_136562.2		n.1284+1751C>T		intron	N/A
	GLP1R	NR_136563.2		n.1284+1751C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLP1R	ENST00000373256.5	TSL:1 MANE Select	c.1224+1751C>T		intron	N/A	ENSP00000362353.4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62258 AN: 151824 Hom.: 12994 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.410 AC: 62297 AN: 151942 Hom.: 13006 Cov.: 32 AF XY: 0.405 AC XY: 30086 AN XY: 74256

African (AFR) AF: 0.479 AC: 19829 AN: 41432

American (AMR) AF: 0.349 AC: 5325 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1960 AN: 5136

South Asian (SAS) AF: 0.353 AC: 1696 AN: 4800

European-Finnish (FIN) AF: 0.371 AC: 3922 AN: 10576

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26907 AN: 67954

Other (OTH) AF: 0.391 AC: 822 AN: 2102

Alfa AF: 0.407 Hom.: 1588

Bravo AF: 0.416

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.92
PhyloP100		-0.067
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: rs2268641; hg19: chr6-39050266;