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GeneBe

6-39079642-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002062.5(GLP1R):c.1122C>T(p.His374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,611,750 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0048 ( 23 hom. )

Consequence

GLP1R
NM_002062.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.18
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 -9 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=-0.3).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-39079642-C-T is Benign according to our data. Variant chr6-39079642-C-T is described in ClinVar as [Benign]. Clinvar id is 774310.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=-2.18 with no splicing effect.
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 505 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLP1RNM_002062.5 linkuse as main transcriptc.1122C>T p.His374= synonymous_variant 11/13 ENST00000373256.5
GLP1RNR_136562.2 linkuse as main transcriptn.1182C>T non_coding_transcript_exon_variant 11/14
GLP1RNR_136563.2 linkuse as main transcriptn.1182C>T non_coding_transcript_exon_variant 11/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLP1RENST00000373256.5 linkuse as main transcriptc.1122C>T p.His374= synonymous_variant 11/131 NM_002062.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00332
AC:
505
AN:
152192
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00528
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00523
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00360
AC:
898
AN:
249250
Hom.:
5
AF XY:
0.00347
AC XY:
468
AN XY:
134802
show subpopulations
Gnomad AFR exome
AF:
0.000863
Gnomad AMR exome
AF:
0.00118
Gnomad ASJ exome
AF:
0.00232
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00132
Gnomad FIN exome
AF:
0.00509
Gnomad NFE exome
AF:
0.00573
Gnomad OTH exome
AF:
0.00395
GnomAD4 exome
AF:
0.00482
AC:
7039
AN:
1459440
Hom.:
23
Cov.:
31
AF XY:
0.00479
AC XY:
3480
AN XY:
726056
show subpopulations
Gnomad4 AFR exome
AF:
0.000780
Gnomad4 AMR exome
AF:
0.00109
Gnomad4 ASJ exome
AF:
0.00273
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00137
Gnomad4 FIN exome
AF:
0.00560
Gnomad4 NFE exome
AF:
0.00564
Gnomad4 OTH exome
AF:
0.00327
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00332
AC:
505
AN:
152310
Hom.:
1
Cov.:
32
AF XY:
0.00333
AC XY:
248
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000986
Gnomad4 AMR
AF:
0.00202
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00528
Gnomad4 NFE
AF:
0.00523
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00446
Hom.:
1
Bravo
AF:
0.00321
EpiCase
AF:
0.00458
EpiControl
AF:
0.00476

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 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
Cadd
Benign
2.2
Dann
Benign
0.59

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: rs12212036; hg19: chr6-39047418; COSMIC: COSV64715338; API