15-69272004-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015554.3(GLCE):c.*2760C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,442 control chromosomes in the GnomAD database, including 23,675 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 0.52 (23586 hom., cov: 32)
  • Exomes 𝑓: 0.64 (89 hom.)
• Consequence: GLCE NM_015554.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCE	NM_015554.3	c.*2760C>T		3_prime_UTR_variant	5/5	ENST00000261858.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCE	ENST00000261858.7	c.*2760C>T		3_prime_UTR_variant	5/5	1	NM_015554.3	P1
GLCE	ENST00000559420.2	c.*2760C>T		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78523 AN: 151892 Hom.: 23584 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.644 AC: 278 AN: 432 Hom.: 89 Cov.: 0 AF XY: 0.669 AC XY: 174 AN XY: 260

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.517 AC: 78523 AN: 152010 Hom.: 23586 Cov.: 32 AF XY: 0.521 AC XY: 38737 AN XY: 74308

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.550

Alfa AF: 0.565 Hom.: 5757

Bravo AF: 0.504

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	20
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6545; hg19: chr15-69564343; COSMIC: COSV55946297; COSMIC: COSV55946297;