2-162146681-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC101929532 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GCG	NM_002054.5	c.254+672A>G		intron_variant		ENST00000418842.7
LOC101929532	NR_110255.1	n.93-15089T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCG	ENST00000418842.7	c.254+672A>G		intron_variant		1	NM_002054.5	P1
GCG	ENST00000375497.3	c.254+672A>G		intron_variant		5		P1
GCG	ENST00000492913.1	n.343+672A>G		intron_variant, non_coding_transcript_variant		2
GCG	ENST00000497568.1	n.41+672A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.00982

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0655

Alfa AF: 0.00646 Hom.: 2

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

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

Other links and lift over

dbSNP: rs4664447; hg19: chr2-163003191;