rs1870050

Variant names:

• chr15-51344354-A-C
• rs1870050
• NM_181789.4:c.363+2307A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51344354-A-C
• chr15-51344354-A-G

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+2307A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,282 control chromosomes in the GnomAD database, including 510 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 0.063 (510 hom., cov: 32)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDN	NM_181789.4	c.363+2307A>C		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+2307A>C		intron_variant	Intron 1 of 9	2	NM_181789.4	ENSP00000335196.6
GLDN	ENST00000558286.5	n.174+2307A>C		intron_variant	Intron 1 of 2	1
GLDN	ENST00000560690.5	n.140+2269A>C		intron_variant	Intron 1 of 3	1
GLDN	ENST00000560215.5	c.249+2307A>C		intron_variant	Intron 1 of 3	4		ENSP00000484633.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9592 AN: 152164 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0630 AC: 9600 AN: 152282 Hom.: 510 Cov.: 32 AF XY: 0.0650 AC XY: 4841 AN XY: 74448

African (AFR) AF: 0.0205 AC: 853 AN: 41570

American (AMR) AF: 0.0870 AC: 1331 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1481 AN: 5170

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4828

European-Finnish (FIN) AF: 0.0843 AC: 893 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4491 AN: 68022

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.0600 Hom.: 47

Bravo AF: 0.0642

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.35
PhyloP100		0.12
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: rs1870050; hg19: chr15-51636551;