rs2445781

Positions:

• chr15-51361063-T-G

Variant summary

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

The NM_181789.4(GLDN):​c.364-16386T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,070 control chromosomes in the GnomAD database, including 9,105 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 0.33 (9105 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.364-16386T>G		intron_variant		ENST00000335449.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.364-16386T>G		intron_variant		2	NM_181789.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49922 AN: 151952 Hom.: 9097 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.329 AC: 49976 AN: 152070 Hom.: 9105 Cov.: 32 AF XY: 0.321 AC XY: 23841 AN XY: 74344

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.321

Alfa AF: 0.300 Hom.: 3899

Bravo AF: 0.357

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.61

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: rs2445781; hg19: chr15-51653260;