dbSNP rs10305420: GLP1R:p.Pro7Arg (chr6-39048860-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002062.5(GLP1R):c.20C>G(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLP1R
NM_002062.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.579

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16104636).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GLP1R	NM_002062.5	MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 13	NP_002053.3
GLP1R	NR_136562.2		n.80C>G		non_coding_transcript_exon	Exon 1 of 14
GLP1R	NR_136563.2		n.80C>G		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLP1R	ENST00000373256.5	TSL:1 MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 13	ENSP00000362353.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1343142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665736

African (AFR)

AF:

0.00

AC:

AN:

27152

American (AMR)

AF:

0.00

AC:

AN:

34170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23688

East Asian (EAS)

AF:

0.00

AC:

AN:

30228

South Asian (SAS)

AF:

0.00

AC:

AN:

75774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4634

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057520

Other (OTH)

AF:

0.00

AC:

AN:

55890

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.24

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

-0.58

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.2

REVEL

Benign

0.050

Sift

Benign

0.94

Sift4G

Benign

0.18

Polyphen

0.53

Vest4

0.18

MutPred

0.38

Gain of MoRF binding (P = 2e-04)

MVP

0.81

MPC

0.49

ClinPred

0.23

GERP RS

1.3

PromoterAI

0.018

Neutral

(source)

Varity_R

0.041

gMVP

0.62

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over