rs2899748

Variant names:

• chr15-69232379-A-G
• rs2899748
• NM_015554.3:c.-14+21973A>G

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+21973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,930 control chromosomes in the GnomAD database, including 23,521 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 0.51 (23521 hom., cov: 31)
• Consequence: GLCE NM_015554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.646 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+21973A>G		intron	N/A	NP_056369.1	O94923
	GLCE	NM_001324093.2		c.-14+21973A>G		intron	N/A	NP_001311022.1	O94923
	GLCE	NM_001324094.2		c.-14+21973A>G		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+21973A>G		intron	N/A	ENSP00000261858.2	O94923
	GLCE	ENST00000897735.1		c.-14+21973A>G		intron	N/A	ENSP00000567794.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78178 AN: 151812 Hom.: 23520 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.515 AC: 78176 AN: 151930 Hom.: 23521 Cov.: 31 AF XY: 0.519 AC XY: 38535 AN XY: 74228

African (AFR) AF: 0.179 AC: 7417 AN: 41444

American (AMR) AF: 0.656 AC: 10021 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2301 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3038 AN: 5154

South Asian (SAS) AF: 0.570 AC: 2742 AN: 4810

European-Finnish (FIN) AF: 0.648 AC: 6823 AN: 10530

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43889 AN: 67940

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.613 Hom.: 14967

Bravo AF: 0.502

Asia WGS AF: 0.498 AC: 1729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.52
PhyloP100		-0.59
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: rs2899748; hg19: chr15-69524718;