Variant 2-162144091-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002054.5(GCG):c.472A>G(p.Ile158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,612,636 control chromosomes in the GnomAD database, including 19 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 18 hom. )

Consequence

GCG
NM_002054.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270

Variant links:

Genes affected

GCG (HGNC:4191): (glucagon) The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon. [provided by RefSeq, Jul 2008]

GCG links:

LOC101929532 (HGNC:):

LOC101929532 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005893886).

BP6

Variant 2-162144091-T-C is Benign according to our data. Variant chr2-162144091-T-C is described in ClinVar as [Benign]. Clinvar id is 718683.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCG	NM_002054.5 linkuse as main transcript	c.472A>G	p.Ile158Val	missense_variant	5/6	ENST00000418842.7
LOC101929532	NR_110255.1 linkuse as main transcript	n.93-17679T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GCG	ENST00000418842.7 linkuse as main transcript	c.472A>G	p.Ile158Val	missense_variant	5/6	1	NM_002054.5	P1
GCG	ENST00000375497.3 linkuse as main transcript	c.472A>G	p.Ile158Val	missense_variant	5/6	5		P1
GCG	ENST00000483769.1 linkuse as main transcript	n.325A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00268

AC:

667

AN:

248640

Hom.:

AF XY:

0.00290

AC XY:

391

AN XY:

134870

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.00845

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00255

AC:

3724

AN:

1460324

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1932

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00634

Gnomad4 FIN exome

AF:

0.00951

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152312

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00782

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00170

AC:

ExAC

AF:

0.00283

AC:

342

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00235

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

Cadd

Benign

0.051

Dann

Benign

0.49

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.050

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.27

MPC

0.034

ClinPred

0.00060

GERP RS

-2.9

Varity_R

0.11

gMVP

0.25

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