rs7175922

Variant names:

• chr15-51354540-G-A
• rs7175922
• NM_181789.4:c.363+12493G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181789.4(GLDN):​c.363+12493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,094 control chromosomes in the GnomAD database, including 6,662 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 (6662 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 10 publications found

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]

GLDN Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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 rank	MANE	Protein	UniProt
GLDN	NM_181789.4	c.363+12493G>A		intron_variant	Intron 1 of 9	ENST00000335449.11	NP_861454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11	c.363+12493G>A		intron_variant	Intron 1 of 9	2	NM_181789.4	ENSP00000335196.6
GLDN	ENST00000558286.5	n.174+12493G>A		intron_variant	Intron 1 of 2	1
GLDN	ENST00000560690.5	n.140+12455G>A		intron_variant	Intron 1 of 3	1
GLDN	ENST00000560215.5	c.249+12493G>A		intron_variant	Intron 1 of 3	4		ENSP00000484633.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36191 AN: 151976 Hom.: 6636 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: 0.207

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.0631

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: 0.239 AC: 36278 AN: 152094 Hom.: 6662 Cov.: 32 AF XY: 0.237 AC XY: 17608 AN XY: 74386

African (AFR) AF: 0.514 AC: 21292 AN: 41398

American (AMR) AF: 0.183 AC: 2791 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5170

South Asian (SAS) AF: 0.274 AC: 1320 AN: 4818

European-Finnish (FIN) AF: 0.0631 AC: 670 AN: 10610

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8028 AN: 68020

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.190 Hom.: 578

Bravo AF: 0.258

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7175922; hg19: chr15-51646737;