rs12148477

Positions:

• chr15-51360922-A-G

Variant summary

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

The NM_181789.4(GLDN):​c.364-16527A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,182 control chromosomes in the GnomAD database, including 5,963 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 0.27 (5963 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDN	NM_181789.4	c.364-16527A>G		intron_variant		ENST00000335449.11	NP_861454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11	c.364-16527A>G		intron_variant		2	NM_181789.4	ENSP00000335196	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41771 AN: 152064 Hom.: 5943 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.275 AC: 41841 AN: 152182 Hom.: 5963 Cov.: 32 AF XY: 0.271 AC XY: 20153 AN XY: 74394

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.274

Alfa AF: 0.292 Hom.: 3659

Bravo AF: 0.290

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.60

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: rs12148477; hg19: chr15-51653119;