rs5987174

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.202

Variant links:

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]

L1CAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	MANE
L1CAM	NM_001278116.2 linkuse as main transcript	c.197+17G>A	intron_variant	ENST00000370060.7
L1CAM	NM_000425.5 linkuse as main transcript	c.197+17G>A	intron_variant
L1CAM	NM_001143963.2 linkuse as main transcript	c.182+17G>A	intron_variant
L1CAM	NM_024003.3 linkuse as main transcript	c.197+17G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L1CAM	ENST00000370060.7 linkuse as main transcript	c.197+17G>A		intron_variant		5	NM_001278116.2	A1	P32004-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

2636

AN:

111073

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

659

AN XY:

33299

show subpopulations

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.:

AF XY:

0.00504

AC XY:

339

AN XY:

67302

show subpopulations

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.:

Cov.:

AF XY:

0.00308

AC XY:

984

AN XY:

319661

show subpopulations

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.:

Cov.:

AF XY:

0.0200

AC XY:

666

AN XY:

33367

show subpopulations

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.:

Bravo

AF:

0.0269

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2013	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over