rs2268641

chr6-39082490-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLP1R	NM_002062.5	c.1224+1751C>T		intron_variant		ENST00000373256.5
GLP1R	NR_136562.2	n.1284+1751C>T		intron_variant, non_coding_transcript_variant
GLP1R	NR_136563.2	n.1284+1751C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLP1R	ENST00000373256.5	c.1224+1751C>T		intron_variant		1	NM_002062.5	P1

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

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.391

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.0
Dann	Benign	0.92

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: rs2268641; hg19: chr6-39050266;