Variant rs6923761 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002062.5(GLP1R):c.502G>A(p.Gly168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,594,086 control chromosomes in the GnomAD database, including 76,319 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4890 hom., cov: 33)

Exomes 𝑓: 0.30 ( 71429 hom. )

Consequence

GLP1R
NM_002062.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.107

Variant links:

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]

GLP1R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050249994).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLP1R	NM_002062.5 linkuse as main transcript	c.502G>A	p.Gly168Ser	missense_variant	5/13	ENST00000373256.5
GLP1R	NR_136562.2 linkuse as main transcript	n.562G>A		non_coding_transcript_exon_variant	5/14
GLP1R	NR_136563.2 linkuse as main transcript	n.562G>A		non_coding_transcript_exon_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLP1R	ENST00000373256.5 linkuse as main transcript	c.502G>A	p.Gly168Ser	missense_variant	5/13	1	NM_002062.5	P1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33293

AN:

152040

Hom.:

4888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.230

AC:

57501

AN:

250114

Hom.:

8297

AF XY:

0.235

AC XY:

31710

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.0574

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.300

AC:

432743

AN:

1441928

Hom.:

71429

Cov.:

AF XY:

0.297

AC XY:

213090

AN XY:

718444

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.00424

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.219

AC:

33287

AN:

152158

Hom.:

4890

Cov.:

AF XY:

0.213

AC XY:

15817

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0615

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.300

Hom.:

17195

Bravo

AF:

0.204

TwinsUK

AF:

0.353

AC:

1310

ALSPAC

AF:

0.360

AC:

1386

ESP6500AA

AF:

0.0656

AC:

289

ESP6500EA

AF:

0.337

AC:

2896

ExAC

AF:

0.232

AC:

28145

Asia WGS

AF:

0.0700

AC:

246

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.17

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.67

REVEL

Benign

0.052

Sift

Benign

0.44

Sift4G

Benign

0.51

Polyphen

0.0010

Vest4

0.023

MPC

0.48

ClinPred

0.0010

GERP RS

-2.1

Varity_R

0.13

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over