rs7176782

Positions:

• chr15-69185041-G-A
• chr15-69185041-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261858.7(GLCE):​c.-105+24284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,080 control chromosomes in the GnomAD database, including 21,458 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 0.49 (21458 hom., cov: 33)
• Consequence: GLCE ENST00000261858.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLCE	NM_015554.3	c.-105+24284G>A		intron_variant		ENST00000261858.7	NP_056369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLCE	ENST00000261858.7	c.-105+24284G>A		intron_variant		1	NM_015554.3	ENSP00000261858	P1
GLCE	ENST00000559798.2	n.175-9395G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74512 AN: 151964 Hom.: 21461 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.490 AC: 74498 AN: 152080 Hom.: 21458 Cov.: 33 AF XY: 0.495 AC XY: 36802 AN XY: 74338

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.521

Alfa AF: 0.597 Hom.: 25879

Bravo AF: 0.478

Asia WGS AF: 0.479 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.54

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: rs7176782; hg19: chr15-69477380; COSMIC: COSV55944890;