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6-39056462-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002062.5(GLP1R):c.144C>G(p.Arg48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,607,600 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 66 hom. )

Consequence

GLP1R
NM_002062.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.439
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 -15 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=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-39056462-C-G is Benign according to our data. Variant chr6-39056462-C-G is described in ClinVar as [Benign]. Clinvar id is 779910.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=-0.439 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00327 (498/152284) while in subpopulation EAS AF= 0.0307 (159/5172). AF 95% confidence interval is 0.0268. There are 10 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 487 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLP1RNM_002062.5 linkuse as main transcriptc.144C>G p.Arg48= synonymous_variant 2/13 ENST00000373256.5
GLP1RNR_136562.2 linkuse as main transcriptn.204C>G non_coding_transcript_exon_variant 2/14
GLP1RNR_136563.2 linkuse as main transcriptn.204C>G non_coding_transcript_exon_variant 2/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLP1RENST00000373256.5 linkuse as main transcriptc.144C>G p.Arg48= synonymous_variant 2/131 NM_002062.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00320
AC:
487
AN:
152166
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0309
Gnomad SAS
AF:
0.0244
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00683
AC:
1715
AN:
251038
Hom.:
17
AF XY:
0.00746
AC XY:
1013
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.000494
Gnomad AMR exome
AF:
0.0113
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0294
Gnomad SAS exome
AF:
0.0238
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00489
GnomAD4 exome
AF:
0.00281
AC:
4088
AN:
1455316
Hom.:
66
Cov.:
28
AF XY:
0.00338
AC XY:
2449
AN XY:
724370
show subpopulations
Gnomad4 AFR exome
AF:
0.000449
Gnomad4 AMR exome
AF:
0.0124
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0284
Gnomad4 SAS exome
AF:
0.0228
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000144
Gnomad4 OTH exome
AF:
0.00426
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00327
AC:
498
AN:
152284
Hom.:
10
Cov.:
32
AF XY:
0.00369
AC XY:
275
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.0107
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0307
Gnomad4 SAS
AF:
0.0244
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.000290
Hom.:
0
Bravo
AF:
0.00396
Asia WGS
AF:
0.0230
AC:
80
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
2.5
Dann
Benign
0.55

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.

Other links and lift over

dbSNP: rs10305437; hg19: chr6-39024238; API