rs1801483

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000160.5(GCGR):c.118G>A(p.Gly40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,536,594 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0083 ( 71 hom. )

Consequence

GCGR
NM_000160.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.712

Variant links:

Genes affected

GCGR (HGNC:4192): (glucagon receptor) The protein encoded by this gene is a glucagon receptor that is important in controlling blood glucose levels. Defects in this gene are a cause of non-insulin-dependent diabetes mellitus (NIDDM).[provided by RefSeq, Jan 2010]

GCGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02872321).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00826 (11438/1384256) while in subpopulation MID AF= 0.0372 (212/5696). AF 95% confidence interval is 0.0331. There are 71 homozygotes in gnomad4_exome. There are 5560 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCGR	NM_000160.5 link	c.118G>A	p.Gly40Ser	missense_variant	Exon 3 of 14	ENST00000400723.8	NP_000151.1	P47871
GCGR	XM_006722277.2 link	c.118G>A	p.Gly40Ser	missense_variant	Exon 3 of 14		XP_006722340.1	P47871
GCGR	XM_017024446.2 link	c.112G>A	p.Gly38Ser	missense_variant	Exon 3 of 14		XP_016879935.1
GCGR	XM_011523539.2 link	c.-109G>A		5_prime_UTR_variant	Exon 1 of 12		XP_011521841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCGR	ENST00000400723.8 link	c.118G>A	p.Gly40Ser	missense_variant	Exon 3 of 14	1	NM_000160.5	ENSP00000383558.3		P47871

Frequencies

GnomAD3 genomes

AF:

0.00646

AC:

983

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00795

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00740

AC:

1049

AN:

141720

Hom.:

AF XY:

0.00753

AC XY:

571

AN XY:

75862

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.00679

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0000942

Gnomad SAS exome

AF:

0.00946

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00855

Gnomad OTH exome

AF:

0.00972

GnomAD4 exome

AF:

0.00826

AC:

11438

AN:

1384256

Hom.:

Cov.:

AF XY:

0.00814

AC XY:

5560

AN XY:

683062

show subpopulations

Gnomad4 AFR exome

AF:

0.00222

Gnomad4 AMR exome

AF:

0.00681

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00775

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00871

Gnomad4 OTH exome

AF:

0.00948

GnomAD4 genome

AF:

0.00645

AC:

982

AN:

152338

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00795

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00994

Hom.:

Bravo

AF:

0.00759

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00582

AC:

142

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GCGR: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Type 2 diabetes mellitus

Benign:1

Feb 01, 1996

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.4

DANN

Benign

0.88

DEOGEN2

Benign

0.034

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.28

T;T;T

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.61

N;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

1.4

N;.;.

REVEL

Benign

0.028

Sift

Benign

0.38

T;.;.

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.10

MVP

0.43

MPC

0.0026

ClinPred

0.00042

GERP RS

-1.3

Varity_R

0.10

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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