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GeneBe

6-39057533-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_002062.5(GLP1R):c.237G>A(p.Ser79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,613,224 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 66 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 49 hom. )

Consequence

GLP1R
NM_002062.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.782
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-39057533-G-A is Benign according to our data. Variant chr6-39057533-G-A is described in ClinVar as [Benign]. Clinvar id is 787828.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.782 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLP1RNM_002062.5 linkuse as main transcriptc.237G>A p.Ser79= synonymous_variant 3/13 ENST00000373256.5
GLP1RNR_136562.2 linkuse as main transcriptn.297G>A non_coding_transcript_exon_variant 3/14
GLP1RNR_136563.2 linkuse as main transcriptn.297G>A non_coding_transcript_exon_variant 3/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLP1RENST00000373256.5 linkuse as main transcriptc.237G>A p.Ser79= synonymous_variant 3/131 NM_002062.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0154
AC:
2349
AN:
152166
Hom.:
66
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0526
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00759
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.00910
GnomAD3 exomes
AF:
0.00436
AC:
1089
AN:
249808
Hom.:
31
AF XY:
0.00316
AC XY:
427
AN XY:
135138
show subpopulations
Gnomad AFR exome
AF:
0.0553
Gnomad AMR exome
AF:
0.00404
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.0000939
Gnomad NFE exome
AF:
0.000416
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.00180
AC:
2627
AN:
1460940
Hom.:
49
Cov.:
31
AF XY:
0.00162
AC XY:
1175
AN XY:
726774
show subpopulations
Gnomad4 AFR exome
AF:
0.0530
Gnomad4 AMR exome
AF:
0.00430
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000813
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.000344
Gnomad4 OTH exome
AF:
0.00404
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0155
AC:
2357
AN:
152284
Hom.:
66
Cov.:
32
AF XY:
0.0148
AC XY:
1105
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0526
Gnomad4 AMR
AF:
0.00758
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00893
Hom.:
14
Bravo
AF:
0.0181
Asia WGS
AF:
0.00606
AC:
21
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000890

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
9.8
Dann
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs10305444; hg19: chr6-39025309; COSMIC: COSV64714503; API