rs17602686

chr15-51377428-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181789.4(GLDN):c.364-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,607,702 control chromosomes in the GnomAD database, including 30,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1994 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28295 hom.)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.67

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 -10 ACMG points.

• BP6: Variant 15-51377428-A-C is Benign according to our data. Variant chr15-51377428-A-C is described in ClinVar as [Benign]. Clinvar id is 1225115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLDN	NM_181789.4	c.364-21A>C		intron_variant		ENST00000335449.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLDN	ENST00000335449.11	c.364-21A>C		intron_variant		2	NM_181789.4	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22284 AN: 152090 Hom.: 1995 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.168 AC: 42143 AN: 250168 Hom.: 3922 AF XY: 0.175 AC XY: 23697 AN XY: 135212

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.0754

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.192 AC: 279871 AN: 1455494 Hom.: 28295 Cov.: 29 AF XY: 0.193 AC XY: 140063 AN XY: 724412

Gnomad4 AFR exome AF: 0.0327

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.146 AC: 22278 AN: 152208 Hom.: 1994 Cov.: 32 AF XY: 0.145 AC XY: 10785 AN XY: 74414

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.174

Alfa AF: 0.181 Hom.: 1011

Bravo AF: 0.140

TwinsUK AF: 0.204 AC: 756

ALSPAC AF: 0.210 AC: 811

ESP6500AA AF: 0.0453 AC: 199

ESP6500EA AF: 0.210 AC: 1805

ExAC AF: 0.169 AC: 20488

Asia WGS AF: 0.141 AC: 490 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	2.5
Dann	Benign	0.79
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0027	T
MutationTaster	Benign	0.0000063	P;P
PROVEAN	Benign	-0.57	N
Sift	Benign	0.50	T
Sift4G	Benign	0.28	T
GERP RS		4.9
La Branchor		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.36		Position offset: 21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17602686; hg19: chr15-51669625; COSMIC: COSV59090383; COSMIC: COSV59090383;