rs12592797

chr15-51347439-C-Achr15-51347439-C-T

Variant summary

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

The NM_181789.4(GLDN):c.363+5392C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,074 control chromosomes in the GnomAD database, including 6,652 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 0.24 (6652 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.363+5392C>A		intron_variant		ENST00000335449.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.363+5392C>A		intron_variant		2	NM_181789.4	P1
GLDN	ENST00000558286.5	n.174+5392C>A		intron_variant, non_coding_transcript_variant		1
GLDN	ENST00000560690.5	n.140+5354C>A		intron_variant, non_coding_transcript_variant		1
GLDN	ENST00000560215.5	c.250+5392C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36144 AN: 151956 Hom.: 6626 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.238 AC: 36233 AN: 152074 Hom.: 6652 Cov.: 32 AF XY: 0.236 AC XY: 17554 AN XY: 74360

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.221

Alfa AF: 0.0722 Hom.: 135

Bravo AF: 0.257

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.5
Dann	Benign	0.57

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: rs12592797; hg19: chr15-51639636;