chr15-69243619-T-C

Variant names:

• chr15-69243619-T-C
• rs11629932
• NM_015554.3:c.-13-12175T>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.-13-12175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,046 control chromosomes in the GnomAD database, including 19,591 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 0.46 (19591 hom., cov: 28)
• Consequence: GLCE NM_015554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.61 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.-13-12175T>C		intron	N/A	NP_056369.1	O94923
	GLCE	NM_001324093.2		c.-13-12175T>C		intron	N/A	NP_001311022.1	O94923
	GLCE	NM_001324094.2		c.-13-12175T>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.-13-12175T>C		intron	N/A	ENSP00000261858.2	O94923
	GLCE	ENST00000897735.1		c.-13-12175T>C		intron	N/A	ENSP00000567794.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70188 AN: 150928 Hom.: 19591 Cov.: 28

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.465 AC: 70176 AN: 151046 Hom.: 19591 Cov.: 28 AF XY: 0.464 AC XY: 34153 AN XY: 73628

African (AFR) AF: 0.147 AC: 6072 AN: 41296

American (AMR) AF: 0.557 AC: 8442 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2179 AN: 3466

East Asian (EAS) AF: 0.346 AC: 1776 AN: 5128

South Asian (SAS) AF: 0.555 AC: 2653 AN: 4784

European-Finnish (FIN) AF: 0.546 AC: 5502 AN: 10070

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.615 AC: 41761 AN: 67856

Other (OTH) AF: 0.503 AC: 1052 AN: 2092

Alfa AF: 0.573 Hom.: 32383

Bravo AF: 0.451

Asia WGS AF: 0.389 AC: 1350 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.51
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11629932;

hg19: chr15-69535958;