NM_000160.5:c.118G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_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. 16/21 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

Publications

54 publications found

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 Gene-Disease associations (from GenCC):

GCGR-related hyperglucagonemia
Inheritance: AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

GCGR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 17-81809839-G-A is Benign according to our data. Variant chr17-81809839-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 16159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 5560 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GCGR	NM_000160.5 link	c.118G>A	p.Gly40Ser	missense_variant	Exon 3 of 14	ENST00000400723.8	NP_000151.1
GCGR	XM_006722277.2 link	c.118G>A	p.Gly40Ser	missense_variant	Exon 3 of 14		XP_006722340.1
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

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

GnomAD2 exomes

AF:

0.00740

AC:

1049

AN:

141720

AF XY:

0.00753

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 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

African (AFR)

AF:

0.00222

AC:

AN:

31594

American (AMR)

AF:

0.00681

AC:

243

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

299

AN:

25182

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35734

South Asian (SAS)

AF:

0.00775

AC:

614

AN:

79234

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

34366

Middle Eastern (MID)

AF:

0.0372

AC:

212

AN:

5696

European-Non Finnish (NFE)

AF:

0.00871

AC:

9401

AN:

1078842

Other (OTH)

AF:

0.00948

AC:

549

AN:

57908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

629

1258

1887

2516

3145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00645

AC:

982

AN:

152338

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41578

American (AMR)

AF:

0.00856

AC:

131

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00477

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00795

AC:

541

AN:

68032

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00819

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

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

- -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.;.

PhyloP100

0.71

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

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over