dbSNP rs7581952: GCG:c.393-176T>G (chr2-162144346-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002054.5(GCG):c.393-176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 585,722 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 479 hom., cov: 32)

Exomes 𝑓: 0.031 ( 849 hom. )

Consequence

GCG
NM_002054.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.146

Publications

4 publications found

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:

ENSG00000236841 (HGNC:):

ENSG00000236841 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCG	NM_002054.5 link	c.393-176T>G		intron_variant	Intron 4 of 5	ENST00000418842.7	NP_002045.1
LOC101929532	NR_110255.1 link	n.93-17424A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GCG	ENST00000418842.7 link	c.393-176T>G	intron_variant	Intron 4 of 5	1	NM_002054.5	ENSP00000387662.2	P01275
GCG	ENST00000483769.1 link	n.70T>G	non_coding_transcript_exon_variant	Exon 1 of 2	2
GCG	ENST00000375497.3 link	c.393-176T>G	intron_variant	Intron 4 of 5	5		ENSP00000364647.3	P01275
ENSG00000236841	ENST00000727531.1 link	n.104-17424A>C	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5637

AN:

152174

Hom.:

470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0488

GnomAD4 exome

AF:

0.0305

AC:

13237

AN:

433430

Hom.:

849

Cov.:

AF XY:

0.0288

AC XY:

6602

AN XY:

228892

show subpopulations

African (AFR)

AF:

0.00843

AC:

103

AN:

12218

American (AMR)

AF:

0.276

AC:

4995

AN:

18112

Ashkenazi Jewish (ASJ)

AF:

0.00681

AC:

AN:

13208

East Asian (EAS)

AF:

0.0178

AC:

545

AN:

30588

South Asian (SAS)

AF:

0.0170

AC:

704

AN:

41504

European-Finnish (FIN)

AF:

0.0164

AC:

468

AN:

28484

Middle Eastern (MID)

AF:

0.00517

AC:

AN:

1934

European-Non Finnish (NFE)

AF:

0.0210

AC:

5506

AN:

262240

Other (OTH)

AF:

0.0325

AC:

816

AN:

25142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

535

1070

1605

2140

2675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0372

AC:

5668

AN:

152292

Hom.:

479

Cov.:

AF XY:

0.0393

AC XY:

2929

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00811

AC:

337

AN:

41570

American (AMR)

AF:

0.222

AC:

3391

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3470

East Asian (EAS)

AF:

0.0202

AC:

105

AN:

5190

South Asian (SAS)

AF:

0.0178

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0120

AC:

128

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0216

AC:

1470

AN:

68010

Other (OTH)

AF:

0.0526

AC:

111

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

243

486

728

971

1214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0289

Hom.:

Bravo

AF:

0.0546

Asia WGS

AF:

0.0560

AC:

196

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.66

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over