rs2899748

Positions:

• chr15-69232379-A-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+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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLCE	NM_015554.3	c.-14+21973A>G		intron_variant		ENST00000261858.7	NP_056369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLCE	ENST00000261858.7	c.-14+21973A>G		intron_variant		1	NM_015554.3	ENSP00000261858	P1

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.546

Alfa AF: 0.614 Hom.: 13314

Bravo AF: 0.502

Asia WGS AF: 0.498 AC: 1729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.52

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: rs2899748; hg19: chr15-69524718;