Variant rs10305420 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.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,492,840 control chromosomes in the GnomAD database, including 99,598 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.28 ( 7298 hom., cov: 33)

Exomes 𝑓: 0.36 ( 92300 hom. )

Consequence

GLP1R
NM_002062.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.579

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019919574).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP1R	NM_002062.5 link	c.20C>T	p.Pro7Leu	missense_variant	1/13	ENST00000373256.5	NP_002053.3	P43220A0A142FHB8
GLP1R	NR_136562.2 link	n.80C>T		non_coding_transcript_exon_variant	1/14
GLP1R	NR_136563.2 link	n.80C>T		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP1R	ENST00000373256.5 link	c.20C>T	p.Pro7Leu	missense_variant	1/13	1	NM_002062.5	ENSP00000362353.4		P43220

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41868

AN:

152062

Hom.:

7296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.314

AC:

36162

AN:

114986

Hom.:

6186

AF XY:

0.314

AC XY:

20706

AN XY:

66020

show subpopulations

Gnomad AFR exome

AF:

0.0733

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.362

AC:

485715

AN:

1340666

Hom.:

92300

Cov.:

AF XY:

0.359

AC XY:

238369

AN XY:

664558

show subpopulations

Gnomad4 AFR exome

AF:

0.0670

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.275

AC:

41860

AN:

152174

Hom.:

7298

Cov.:

AF XY:

0.275

AC XY:

20456

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0772

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.331

Hom.:

1897

Bravo

AF:

0.259

TwinsUK

AF:

0.401

AC:

1487

ALSPAC

AF:

0.377

AC:

1454

ESP6500AA

AF:

0.0627

AC:

186

ESP6500EA

AF:

0.306

AC:

2034

ExAC

AF:

0.263

AC:

27569

Asia WGS

AF:

0.155

AC:

540

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.25

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

REVEL

Benign

0.050

Sift

Benign

0.42

Sift4G

Benign

0.071

Polyphen

0.0010

Vest4

0.073

MPC

0.47

ClinPred

0.0056

GERP RS

1.3

Varity_R

0.031

gMVP

0.45

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