2-162146681-T-C

Variant names:

• chr2-162146681-T-C
• rs4664447
• NM_002054.5:c.254+672A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002054.5(GCG):​c.254+672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 151,958 control chromosomes in the GnomAD database, including 714 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 0.048 (714 hom., cov: 32)
• Consequence: GCG NM_002054.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 7 publications found

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]

ENSG00000236841 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCG	NM_002054.5	c.254+672A>G		intron_variant	Intron 3 of 5	ENST00000418842.7	NP_002045.1
LOC101929532	NR_110255.1	n.93-15089T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCG	ENST00000418842.7	c.254+672A>G		intron_variant	Intron 3 of 5	1	NM_002054.5	ENSP00000387662.2

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7241 AN: 151840 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0479 AC: 7274 AN: 151958 Hom.: 714 Cov.: 32 AF XY: 0.0513 AC XY: 3813 AN XY: 74260

African (AFR) AF: 0.0117 AC: 486 AN: 41476

American (AMR) AF: 0.244 AC: 3717 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00982 AC: 34 AN: 3462

East Asian (EAS) AF: 0.209 AC: 1071 AN: 5118

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4822

European-Finnish (FIN) AF: 0.0122 AC: 129 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1493 AN: 67962

Other (OTH) AF: 0.0655 AC: 138 AN: 2106

Alfa AF: 0.0308 Hom.: 290

Bravo AF: 0.0689

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4664447; hg19: chr2-163003191;