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6-39072917-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002062.5(GLP1R):c.565C>T(p.Leu189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,062 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 17 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 18 hom. )

Consequence

GLP1R
NM_002062.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.32
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=-0.29).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-39072917-C-T is Benign according to our data. Variant chr6-39072917-C-T is described in ClinVar as [Benign]. Clinvar id is 789746.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=3.32 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00819 (1247/152342) while in subpopulation AFR AF= 0.0269 (1117/41578). AF 95% confidence interval is 0.0256. There are 17 homozygotes in gnomad4. There are 604 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1244 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLP1RNM_002062.5 linkuse as main transcriptc.565C>T p.Leu189= synonymous_variant 6/13 ENST00000373256.5
GLP1RNR_136562.2 linkuse as main transcriptn.625C>T non_coding_transcript_exon_variant 6/14
GLP1RNR_136563.2 linkuse as main transcriptn.625C>T non_coding_transcript_exon_variant 6/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLP1RENST00000373256.5 linkuse as main transcriptc.565C>T p.Leu189= synonymous_variant 6/131 NM_002062.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00817
AC:
1244
AN:
152222
Hom.:
17
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0269
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00530
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00717
GnomAD3 exomes
AF:
0.00237
AC:
596
AN:
251432
Hom.:
10
AF XY:
0.00174
AC XY:
237
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0286
Gnomad AMR exome
AF:
0.00228
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000308
Gnomad OTH exome
AF:
0.00244
GnomAD4 exome
AF:
0.00101
AC:
1475
AN:
1461720
Hom.:
18
Cov.:
32
AF XY:
0.000960
AC XY:
698
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.0279
Gnomad4 AMR exome
AF:
0.00271
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000234
Gnomad4 OTH exome
AF:
0.00215
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00819
AC:
1247
AN:
152342
Hom.:
17
Cov.:
33
AF XY:
0.00811
AC XY:
604
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0269
Gnomad4 AMR
AF:
0.00529
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00547
Hom.:
4
Bravo
AF:
0.00932
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000237

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 testingInvitaeJul 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
Cadd
Benign
10
Dann
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs10305474; hg19: chr6-39040693; API