Variant 6-39079642-C-T details in Genebe, Genetics Data Aggregator

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

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]

GLP1R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

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

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BS2

High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GLP1R	NM_002062.5 linkuse as main transcript	c.1122C>T	p.His374=	synonymous_variant	11/13	ENST00000373256.5	NP_002053.3
GLP1R	NR_136562.2 linkuse as main transcript	n.1182C>T		non_coding_transcript_exon_variant	11/14
GLP1R	NR_136563.2 linkuse as main transcript	n.1182C>T		non_coding_transcript_exon_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP1R	ENST00000373256.5 linkuse as main transcript	c.1122C>T	p.His374=	synonymous_variant	11/13	1	NM_002062.5	ENSP00000362353	P1

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

505

AN:

152192

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00332

AC:

505

AN:

152310

Hom.:

Cov.:

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.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over