Variant 17-81809071-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.53C>A(p.Ala18Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,535,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

GCGR
NM_000160.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.360

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=0.09195301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/14	ENST00000400723.8	NP_000151.1	P47871
GCGR	XM_006722277.2 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/14		XP_006722340.1	P47871
GCGR	XM_017024446.2 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/14		XP_016879935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GCGR	ENST00000400723.8 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/14	1	NM_000160.5	ENSP00000383558.3	P47871
GCGR	ENST00000572185.1 linkuse as main transcript	n.348C>A		non_coding_transcript_exon_variant	2/3	1
GCGR	ENST00000570996.5 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/12	2		ENSP00000460976.1	I3L454
GCGR	ENST00000573428.1 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	2/4	4		ENSP00000458930.1	I3L1L8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

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:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000725

AC:

AN:

137886

Hom.:

AF XY:

0.0000135

AC XY:

AN XY:

73866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1383648

Hom.:

Cov.:

AF XY:

0.00000732

AC XY:

AN XY:

682708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

May 25, 2022

The c.53C>A (p.A18D) alteration is located in exon 2 (coding exon 1) of the GCGR gene. This alteration results from a C to A substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.6

DANN

Benign

0.67

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.40

T;T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.034

Sift

Benign

0.11

T;.;.

Sift4G

Benign

0.53

T;D;T

Polyphen

0.089

B;.;.

Vest4

0.19

MutPred

0.55

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.54

MPC

0.0023

ClinPred

0.051

GERP RS

-1.9

Varity_R

0.14

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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