Variant 2-162147348-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002054.5(GCG):c.254+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00585 in 1,610,428 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 56 hom. )

Consequence

GCG
NM_002054.5 splice_region, intron

Scores

Splicing: ADA: 0.9996

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.51

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:

GCG (HGNC:):

GCG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-162147348-C-T is Benign according to our data. Variant chr2-162147348-C-T is described in ClinVar as [Benign]. Clinvar id is 711801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00609 (8886/1458166) while in subpopulation EAS AF= 0.0239 (946/39630). AF 95% confidence interval is 0.0226. There are 56 homozygotes in gnomad4_exome. There are 4581 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCG	NM_002054.5 linkuse as main transcript	c.254+5G>A		splice_region_variant, intron_variant		ENST00000418842.7	NP_002045.1
LOC101929532	NR_110255.1 linkuse as main transcript	n.93-14422C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GCG	ENST00000418842.7 linkuse as main transcript	c.254+5G>A	splice_region_variant, intron_variant	1	NM_002054.5	ENSP00000387662.2	P01275
GCG	ENST00000375497.3 linkuse as main transcript	c.254+5G>A	splice_region_variant, intron_variant	5		ENSP00000364647.3	P01275
GCG	ENST00000492913.1 linkuse as main transcript	n.343+5G>A	splice_region_variant, intron_variant	2
GCG	ENST00000497568.1 linkuse as main transcript	n.41+5G>A	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

537

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00428

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00550

AC:

1364

AN:

247922

Hom.:

AF XY:

0.00600

AC XY:

807

AN XY:

134452

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.00885

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.000793

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00665

GnomAD4 exome

AF:

0.00609

AC:

8886

AN:

1458166

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

4581

AN XY:

725318

show subpopulations

Gnomad4 AFR exome

AF:

0.000809

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.00708

Gnomad4 EAS exome

AF:

0.0239

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00550

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152262

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

249

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00428

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.00347

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.87

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