rs910171

Variant names:

• chr6-39051098-G-C
• rs910171
• NM_002062.5:c.78+2180G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLP1R	NM_002062.5	MANE Select	c.78+2180G>C		intron	N/A	NP_002053.3
	GLP1R	NR_136562.2		n.138+2180G>C		intron	N/A
	GLP1R	NR_136563.2		n.138+2180G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLP1R	ENST00000373256.5	TSL:1 MANE Select	c.78+2180G>C		intron	N/A	ENSP00000362353.4	P43220

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

African (AFR) AF: 0.226 AC: 9352 AN: 41470

American (AMR) AF: 0.179 AC: 2745 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5176

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4822

European-Finnish (FIN) AF: 0.0272 AC: 289 AN: 10624

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0521 AC: 3542 AN: 68024

Other (OTH) AF: 0.104 AC: 219 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		0.14
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: rs910171; hg19: chr6-39018874;