chrX-153864303-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001278116.2(L1CAM):​c.3322+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,205,574 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000016 ( 0 hom. 7 hem. )

Consequence

L1CAM
NM_001278116.2 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.06

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant X-153864303-C-T is Benign according to our data. Variant chrX-153864303-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
L1CAMNM_001278116.2 linkc.3322+19G>A intron_variant Intron 25 of 28 ENST00000370060.7 NP_001265045.1 P32004-1
L1CAMNM_000425.5 linkc.3322+19G>A intron_variant Intron 24 of 27 NP_000416.1 P32004-1
L1CAMNM_024003.3 linkc.3322+19G>A intron_variant Intron 24 of 26 NP_076493.1 P32004-2
L1CAMNM_001143963.2 linkc.3307+19G>A intron_variant Intron 23 of 25 NP_001137435.1 P32004-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
L1CAMENST00000370060.7 linkc.3322+19G>A intron_variant Intron 25 of 28 5 NM_001278116.2 ENSP00000359077.1 P32004-1

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112345
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.0000647
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000276
AC:
5
AN:
181277
AF XY:
0.0000302
show subpopulations
Gnomad AFR exome
AF:
0.000229
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000156
AC:
17
AN:
1093229
Hom.:
0
Cov.:
31
AF XY:
0.0000195
AC XY:
7
AN XY:
359379
show subpopulations
African (AFR)
AF:
0.000152
AC:
4
AN:
26320
American (AMR)
AF:
0.00
AC:
0
AN:
35199
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19359
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30188
South Asian (SAS)
AF:
0.0000555
AC:
3
AN:
54066
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
39304
Middle Eastern (MID)
AF:
0.000269
AC:
1
AN:
3719
European-Non Finnish (NFE)
AF:
0.00000953
AC:
8
AN:
839132
Other (OTH)
AF:
0.0000218
AC:
1
AN:
45942
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000178
AC:
2
AN:
112345
Hom.:
0
Cov.:
24
AF XY:
0.0000290
AC XY:
1
AN XY:
34515
show subpopulations
African (AFR)
AF:
0.0000647
AC:
2
AN:
30923
American (AMR)
AF:
0.00
AC:
0
AN:
10705
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2652
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3573
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2736
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6219
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
234
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53099
Other (OTH)
AF:
0.00
AC:
0
AN:
1517
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Nov 22, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Spastic paraplegia Benign:1
Apr 25, 2024
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
-0.92
CADD
Benign
0.066
DANN
Benign
0.50
PhyloP100
-3.1
PromoterAI
-0.00010
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs375076231; hg19: chrX-153129758; API