rs7581952

Positions:

• chr2-162144346-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418842.7(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 ENST00000418842.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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 -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/exons	MANE	Protein	UniProt
GCG	NM_002054.5	c.393-176T>G		intron_variant		ENST00000418842.7	NP_002045.1
LOC101929532	NR_110255.1	n.93-17424A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCG	ENST00000418842.7	c.393-176T>G		intron_variant		1	NM_002054.5	ENSP00000387662	P1
GCG	ENST00000375497.3	c.393-176T>G		intron_variant		5		ENSP00000364647	P1
GCG	ENST00000483769.1	n.70T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5637 AN: 152174 Hom.: 470 Cov.: 32

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.: 4 AF XY: 0.0288 AC XY: 6602 AN XY: 228892

Gnomad4 AFR exome AF: 0.00843

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.00681

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0210

Gnomad4 OTH exome AF: 0.0325

GnomAD4 genome AF: 0.0372 AC: 5668 AN: 152292 Hom.: 479 Cov.: 32 AF XY: 0.0393 AC XY: 2929 AN XY: 74464

Gnomad4 AFR AF: 0.00811

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0289 Hom.: 33

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
DANN	Benign	0.66

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: rs7581952; hg19: chr2-163000856;