Variant rs1042044 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.780A>C(p.Leu260Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,212 control chromosomes in the GnomAD database, including 257,118 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.56 ( 24439 hom., cov: 31)

Exomes 𝑓: 0.56 ( 232679 hom. )

Consequence

GLP1R
NM_002062.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.656

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:

GLP1R (HGNC:):

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=9.427291E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP1R	NM_002062.5 linkuse as main transcript	c.780A>C	p.Leu260Phe	missense_variant	7/13	ENST00000373256.5	NP_002053.3	P43220A0A142FHB8
GLP1R	NR_136562.2 linkuse as main transcript	n.840A>C		non_coding_transcript_exon_variant	7/14
GLP1R	NR_136563.2 linkuse as main transcript	n.840A>C		non_coding_transcript_exon_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP1R	ENST00000373256.5 linkuse as main transcript	c.780A>C	p.Leu260Phe	missense_variant	7/13	1	NM_002062.5	ENSP00000362353.4		P43220

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85637

AN:

151860

Hom.:

24400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.557

GnomAD3 exomes

AF:

0.565

AC:

141904

AN:

251338

Hom.:

40227

AF XY:

0.563

AC XY:

76532

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.580

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.563

Gnomad SAS exome

AF:

0.576

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.567

GnomAD4 exome

AF:

0.563

AC:

823257

AN:

1461234

Hom.:

232679

Cov.:

AF XY:

0.563

AC XY:

409577

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.456

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.566

Gnomad4 OTH exome

AF:

0.555

GnomAD4 genome

AF:

0.564

AC:

85734

AN:

151978

Hom.:

24439

Cov.:

AF XY:

0.563

AC XY:

41848

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.547

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.563

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.555

Hom.:

59820

Bravo

AF:

0.566

ESP6500AA

AF:

0.580

AC:

2557

ESP6500EA

AF:

0.559

AC:

4806

ExAC

AF:

0.564

AC:

68424

EpiCase

AF:

0.566

EpiControl

AF:

0.551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.080

DEOGEN2

Benign

0.19

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.25

MetaRNN

Benign

0.000094

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

3.4

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MutPred

0.56

Gain of glycosylation at S258 (P = 0.1894);

MPC

0.51

ClinPred

0.0022

GERP RS

3.9

Varity_R

0.063

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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