Variant 17-81810923-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000160.5(GCGR):c.262C>A(p.His88Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,535,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

GCGR
NM_000160.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.702

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:

GCGR (HGNC:):

GCGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23605022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5 linkuse as main transcript	c.262C>A	p.His88Asn	missense_variant	4/14	ENST00000400723.8	NP_000151.1	P47871
GCGR	XM_006722277.2 linkuse as main transcript	c.262C>A	p.His88Asn	missense_variant	4/14		XP_006722340.1	P47871
GCGR	XM_017024446.2 linkuse as main transcript	c.256C>A	p.His86Asn	missense_variant	4/14		XP_016879935.1
GCGR	XM_011523539.2 linkuse as main transcript	c.172+14C>A		intron_variant			XP_011521841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GCGR	ENST00000400723.8 linkuse as main transcript	c.262C>A	p.His88Asn	missense_variant	4/14	1	NM_000160.5	ENSP00000383558.3	P47871
GCGR	ENST00000570996.5 linkuse as main transcript	c.262C>A	p.His88Asn	missense_variant	4/12	2		ENSP00000460976.1	I3L454
GCGR	ENST00000574283.2 linkuse as main transcript	n.346C>A		non_coding_transcript_exon_variant	2/3	5
GCGR	ENST00000573428.1 linkuse as main transcript	c.*22C>A		downstream_gene_variant		4		ENSP00000458930.1	I3L1L8

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000141

AC:

AN:

141856

Hom.:

AF XY:

0.0000264

AC XY:

AN XY:

75892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000679

AC:

AN:

1383840

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

682884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000825

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000243

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.262C>A (p.H88N) alteration is located in exon 4 (coding exon 3) of the GCGR gene. This alteration results from a C to A substitution at nucleotide position 262, causing the histidine (H) at amino acid position 88 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.65

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.1

D;.

REVEL

Benign

0.13

Sift

Benign

0.10

T;.

Sift4G

Benign

0.24

T;T

Polyphen

0.0070

B;.

Vest4

0.36

MutPred

0.56

Gain of MoRF binding (P = 0.0963);Gain of MoRF binding (P = 0.0963);

MVP

0.64

MPC

0.0026

ClinPred

0.069

GERP RS

0.081

Varity_R

0.48

gMVP

0.73

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