rs2229611

Variant names:

• chr17-42911449-T-C
• rs2229611
• NM_000151.4:c.*23T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-42911449-T-C
• chr17-42911449-T-A
• chr17-42911449-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000151.4(G6PC1):​c.*23T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,613,692 control chromosomes in the GnomAD database, including 467,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40789 hom., cov: 31)
  • Exomes 𝑓: 0.76 (426315 hom.)
• Consequence: G6PC1 NM_000151.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.696
• Publications: 39 publications found

Genes affected

G6PC1 (HGNC:4056): (glucose-6-phosphatase catalytic subunit 1) Glucose-6-phosphatase (G6Pase) is a multi-subunit integral membrane protein of the endoplasmic reticulum that is composed of a catalytic subunit and transporters for G6P, inorganic phosphate, and glucose. This gene (G6PC) is one of the three glucose-6-phosphatase catalytic-subunit-encoding genes in human: G6PC, G6PC2 and G6PC3. Glucose-6-phosphatase catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose and orthophosphate and is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis. Mutations in this gene cause glycogen storage disease type I (GSD1). This disease, also known as von Gierke disease, is a metabolic disorder characterized by severe hypoglycemia associated with the accumulation of glycogen and fat in the liver and kidneys.[provided by RefSeq, Feb 2011]

G6PC1 Gene-Disease associations (from GenCC):

• glycogen storage disease due to glucose-6-phosphatase deficiency type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women's Health, Labcorp Genetics (formerly Invitae)
• glycogen storage disease I

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-42911449-T-C is Benign according to our data. Variant chr17-42911449-T-C is described in ClinVar as Benign. ClinVar VariationId is 255350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000151.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC1	NM_000151.4	MANE Select	c.*23T>C		3_prime_UTR	Exon 5 of 5	NP_000142.2	P35575-1
	G6PC1	NM_001270397.2		c.*489T>C		3_prime_UTR	Exon 5 of 5	NP_001257326.1	P35575-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC1	ENST00000253801.7	TSL:1 MANE Select	c.*23T>C		3_prime_UTR	Exon 5 of 5	ENSP00000253801.1	P35575-1
	G6PC1	ENST00000887113.1		c.*23T>C		3_prime_UTR	Exon 5 of 5	ENSP00000557172.1
	G6PC1	ENST00000887112.1		c.*23T>C		3_prime_UTR	Exon 5 of 5	ENSP00000557171.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110626 AN: 151990 Hom.: 40789 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.732

GnomAD2 exomes AF: 0.708 AC: 176095 AN: 248560 AF XY: 0.714

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.575

Gnomad ASJ exome AF: 0.778

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.783

Gnomad OTH exome AF: 0.734

GnomAD4 exome AF: 0.760 AC: 1110785 AN: 1461584 Hom.: 426315 Cov.: 58 AF XY: 0.758 AC XY: 551463 AN XY: 727110

African (AFR) AF: 0.687 AC: 23006 AN: 33480

American (AMR) AF: 0.584 AC: 26116 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 20276 AN: 26136

East Asian (EAS) AF: 0.446 AC: 17719 AN: 39698

South Asian (SAS) AF: 0.654 AC: 56409 AN: 86220

European-Finnish (FIN) AF: 0.815 AC: 43384 AN: 53254

Middle Eastern (MID) AF: 0.719 AC: 4149 AN: 5768

European-Non Finnish (NFE) AF: 0.787 AC: 874766 AN: 1111922

Other (OTH) AF: 0.744 AC: 44960 AN: 60390

GnomAD4 genome AF: 0.727 AC: 110656 AN: 152108 Hom.: 40789 Cov.: 31 AF XY: 0.721 AC XY: 53647 AN XY: 74362

African (AFR) AF: 0.687 AC: 28521 AN: 41486

American (AMR) AF: 0.624 AC: 9527 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2706 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2352 AN: 5172

South Asian (SAS) AF: 0.638 AC: 3071 AN: 4810

European-Finnish (FIN) AF: 0.816 AC: 8631 AN: 10582

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53235 AN: 67994

Other (OTH) AF: 0.732 AC: 1545 AN: 2112

Alfa AF: 0.760 Hom.: 197803

Bravo AF: 0.714

Asia WGS AF: 0.560 AC: 1950 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (4)
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2229611;

hg19: chr17-41063466;

COSMIC: COSV53829988;

COSMIC: COSV53829988;