17-81810888-C-T

Position:

chr17-81810888-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000160.5(GCGR):c.227C>T(p.Thr76Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,536,354 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 2 hom. )

Consequence

GCGR
NM_000160.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.34

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03993988).

BP6

Variant 17-81810888-C-T is Benign according to our data. Variant chr17-81810888-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1545432.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5 linkuse as main transcript	c.227C>T	p.Thr76Met	missense_variant	4/14	ENST00000400723.8	NP_000151.1	P47871
GCGR	XM_006722277.2 linkuse as main transcript	c.227C>T	p.Thr76Met	missense_variant	4/14		XP_006722340.1	P47871
GCGR	XM_017024446.2 linkuse as main transcript	c.221C>T	p.Thr74Met	missense_variant	4/14		XP_016879935.1
GCGR	XM_011523539.2 linkuse as main transcript	c.151C>T	p.Arg51Trp	missense_variant	2/12		XP_011521841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GCGR	ENST00000400723.8 linkuse as main transcript	c.227C>T	p.Thr76Met	missense_variant	4/14	1	NM_000160.5	ENSP00000383558.3	P47871
GCGR	ENST00000570996.5 linkuse as main transcript	c.227C>T	p.Thr76Met	missense_variant	4/12	2		ENSP00000460976.1	I3L454
GCGR	ENST00000573428.1 linkuse as main transcript	c.227C>T	p.Thr76Met	missense_variant	4/4	4		ENSP00000458930.1	I3L1L8
GCGR	ENST00000574283.2 linkuse as main transcript	n.311C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000855

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00132

AC:

188

AN:

141948

Hom.:

AF XY:

0.00124

AC XY:

AN XY:

75918

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00215

AC:

2976

AN:

1384454

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1401

AN XY:

683184

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00183

GnomAD4 genome

AF:

0.00150

AC:

228

AN:

151900

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

117

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000855

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000354

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.227C>T (p.T76M) alteration is located in exon 4 (coding exon 3) of the GCGR gene. This alteration results from a C to T substitution at nucleotide position 227, causing the threonine (T) at amino acid position 76 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;.

Eigen

Benign

-0.024

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.5

D;.;.

REVEL

Benign

0.22

Sift

Benign

0.16

T;.;.

Sift4G

Benign

0.067

T;T;D

Polyphen

1.0

D;.;.

Vest4

0.21

MVP

0.83

MPC

0.0086

ClinPred

0.36

GERP RS

3.2

Varity_R

0.094

gMVP

0.58

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