X-153872575-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:6

Conservation

PhyloP100: -0.202

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

L1 syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
MASA syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
X-linked complicated corpus callosum dysgenesis
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
X-linked complicated spastic paraplegia type 1
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

L1CAM links:

ENSG00000284987 (HGNC:):

ENSG00000284987 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 92921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
L1CAM	NM_001278116.2 link	c.197+17G>A	intron_variant	Intron 4 of 28	ENST00000370060.7	NP_001265045.1
L1CAM	NM_000425.5 link	c.197+17G>A	intron_variant	Intron 3 of 27		NP_000416.1
L1CAM	NM_024003.3 link	c.197+17G>A	intron_variant	Intron 3 of 26		NP_076493.1
L1CAM	NM_001143963.2 link	c.182+17G>A	intron_variant	Intron 2 of 25		NP_001137435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L1CAM	ENST00000370060.7 link	c.197+17G>A		intron_variant	Intron 4 of 28	5	NM_001278116.2	ENSP00000359077.1
ENSG00000284987	ENST00000646191.1 link	n.*239+17G>A		intron_variant	Intron 4 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

2636

AN:

111073

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00748

AC:

1367

AN:

182710

AF XY:

0.00504

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 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

African (AFR)

AF:

0.0791

AC:

2002

AN:

25316

American (AMR)

AF:

0.00495

AC:

174

AN:

35130

Ashkenazi Jewish (ASJ)

AF:

0.00858

AC:

163

AN:

19008

East Asian (EAS)

AF:

0.000167

AC:

AN:

29988

South Asian (SAS)

AF:

0.000284

AC:

AN:

52824

European-Finnish (FIN)

AF:

0.000124

AC:

AN:

40464

Middle Eastern (MID)

AF:

0.00375

AC:

AN:

4005

European-Non Finnish (NFE)

AF:

0.00119

AC:

936

AN:

788069

Other (OTH)

AF:

0.00693

AC:

306

AN:

44187

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

135

270

405

540

675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0239

AC:

2651

AN:

111131

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

666

AN XY:

33367

show subpopulations

African (AFR)

AF:

0.0792

AC:

2420

AN:

30560

American (AMR)

AF:

0.00859

AC:

AN:

10474

Ashkenazi Jewish (ASJ)

AF:

0.00757

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3495

South Asian (SAS)

AF:

0.000391

AC:

AN:

2555

European-Finnish (FIN)

AF:

0.000165

AC:

AN:

6065

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00155

AC:

AN:

52944

Other (OTH)

AF:

0.0247

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

176

263

351

439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0269

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 01, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic paraplegia

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

(source)

DANN

Benign

0.30

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over