15-51360996-G-T

Variant summary

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

The NM_181789.4(GLDN):c.364-16453G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,212 control chromosomes in the GnomAD database, including 2,220 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 0.15 (2220 hom., cov: 33)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

Genes affected

GLDN (HGNC:29514): (gliomedin) This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.364-16453G>T		intron_variant		ENST00000335449.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.364-16453G>T		intron_variant		2	NM_181789.4	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23450 AN: 152094 Hom.: 2221 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.154 AC: 23458 AN: 152212 Hom.: 2220 Cov.: 33 AF XY: 0.151 AC XY: 11240 AN XY: 74418

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.160

Alfa AF: 0.177 Hom.: 1139

Bravo AF: 0.162

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.84
Dann	Benign	0.37

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: rs12148492; hg19: chr15-51653193;