15-69215121-T-C

Variant names:

• chr15-69215121-T-C
• rs4777126
• NM_015554.3:c.-14+4715T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015554.3. 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
	GLCE	NM_015554.3	MANE Select	c.-14+4715T>C		intron	N/A	NP_056369.1	O94923
	GLCE	NM_001324093.2		c.-14+4715T>C		intron	N/A	NP_001311022.1	O94923
	GLCE	NM_001324094.2		c.-14+4715T>C		intron	N/A	NP_001311023.1	O94923

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCE	ENST00000261858.7	TSL:1 MANE Select	c.-14+4715T>C		intron	N/A	ENSP00000261858.2	O94923
	GLCE	ENST00000897735.1		c.-14+4715T>C		intron	N/A	ENSP00000567794.1

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

African (AFR) AF: 0.271 AC: 11244 AN: 41428

American (AMR) AF: 0.816 AC: 12452 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3776 AN: 5154

South Asian (SAS) AF: 0.768 AC: 3701 AN: 4820

European-Finnish (FIN) AF: 0.876 AC: 9276 AN: 10588

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60321 AN: 67970

Other (OTH) AF: 0.735 AC: 1553 AN: 2112

Alfa AF: 0.829 Hom.: 98663

Bravo AF: 0.676

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.0
DANN	Benign	0.92
PhyloP100		-0.91
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: rs4777126; hg19: chr15-69507460;