rs5987174

Positions:

• chrX-153872575-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001278116.2(L1CAM):​c.197+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,150,122 control chromosomes in the GnomAD database, including 162 homozygotes. There are 1,650 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (76 hom., 666 hem., cov: 23)
  • Exomes 𝑓: 0.0035 (86 hom. 984 hem.)
• Consequence: L1CAM NM_001278116.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.202

Genes affected

L1CAM (HGNC:6470): (L1 cell adhesion molecule) The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-153872575-C-T is Benign according to our data. Variant chrX-153872575-C-T is described in ClinVar as [Benign]. Clinvar id is 92921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153872575-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L1CAM	NM_001278116.2	c.197+17G>A		intron_variant		ENST00000370060.7	NP_001265045.1
L1CAM	NM_000425.5	c.197+17G>A		intron_variant			NP_000416.1
L1CAM	NM_001143963.2	c.182+17G>A		intron_variant			NP_001137435.1
L1CAM	NM_024003.3	c.197+17G>A		intron_variant			NP_076493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L1CAM	ENST00000370060.7	c.197+17G>A		intron_variant		5	NM_001278116.2	ENSP00000359077	A1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 2636 AN: 111073 Hom.: 75 Cov.: 23 AF XY: 0.0198 AC XY: 659 AN XY: 33299

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00860

Gnomad ASJ AF: 0.00757

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000390

Gnomad FIN AF: 0.000165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.0251

GnomAD3 exomes AF: 0.00748 AC: 1367 AN: 182710 Hom.: 43 AF XY: 0.00504 AC XY: 339 AN XY: 67302

Gnomad AFR exome AF: 0.0812

Gnomad AMR exome AF: 0.00456

Gnomad ASJ exome AF: 0.00804

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.000367

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00349 AC: 3621 AN: 1038991 Hom.: 86 Cov.: 26 AF XY: 0.00308 AC XY: 984 AN XY: 319661

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.00495

Gnomad4 ASJ exome AF: 0.00858

Gnomad4 EAS exome AF: 0.000167

Gnomad4 SAS exome AF: 0.000284

Gnomad4 FIN exome AF: 0.000124

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00693

GnomAD4 genome AF: 0.0239 AC: 2651 AN: 111131 Hom.: 76 Cov.: 23 AF XY: 0.0200 AC XY: 666 AN XY: 33367

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.00859

Gnomad4 ASJ AF: 0.00757

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000391

Gnomad4 FIN AF: 0.000165

Gnomad4 NFE AF: 0.00155

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0139 Hom.: 75

Bravo AF: 0.0269

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 01, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.19
DANN	Benign	0.30

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: rs5987174; hg19: chrX-153138030; COSMIC: COSV62830249; COSMIC: COSV62830249;