rs4777126

chr15-69215121-T-Cchr15-69215121-T-G

Variant summary

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

The NM_015554.3(GLCE):c.-14+4715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,014 control chromosomes in the GnomAD database, including 42,920 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 0.70 (42920 hom., cov: 31)
• Consequence: GLCE NM_015554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

Genes affected

GLCE (HGNC:17855): (glucuronic acid epimerase) Enables calcium ion binding activity; heparosan-N-sulfate-glucuronate 5-epimerase activity; and protein homodimerization activity. Involved in heparan sulfate proteoglycan biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCE	NM_015554.3	c.-14+4715T>C		intron_variant		ENST00000261858.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCE	ENST00000261858.7	c.-14+4715T>C		intron_variant		1	NM_015554.3	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106516 AN: 151896 Hom.: 42922 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.701 AC: 106522 AN: 152014 Hom.: 42920 Cov.: 31 AF XY: 0.704 AC XY: 52341 AN XY: 74314

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.735

Alfa AF: 0.852 Hom.: 73715

Bravo AF: 0.676

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.0
Dann	Benign	0.92

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: rs4777126; hg19: chr15-69507460;