rs910171

Positions:

• chr6-39051098-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002062.5(GLP1R):​c.78+2180G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,198 control chromosomes in the GnomAD database, including 1,504 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 0.11 (1504 hom., cov: 32)
• Consequence: GLP1R NM_002062.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP1R	NM_002062.5	c.78+2180G>C		intron_variant		ENST00000373256.5	NP_002053.3
GLP1R	NR_136562.2	n.138+2180G>C		intron_variant, non_coding_transcript_variant
GLP1R	NR_136563.2	n.138+2180G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP1R	ENST00000373256.5	c.78+2180G>C		intron_variant		1	NM_002062.5	ENSP00000362353	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16761 AN: 152082 Hom.: 1492 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.110 AC: 16808 AN: 152198 Hom.: 1504 Cov.: 32 AF XY: 0.110 AC XY: 8189 AN XY: 74422

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0521

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0887 Hom.: 122

Bravo AF: 0.128

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.54

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: rs910171; hg19: chr6-39018874;