X-153863865-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001278116.2(L1CAM):​c.3457+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 24)

Consequence

L1CAM
NM_001278116.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.32
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
L1CAMNM_001278116.2 linkc.3457+18C>A intron_variant Intron 26 of 28 ENST00000370060.7 NP_001265045.1 P32004-1
L1CAMNM_000425.5 linkc.3457+18C>A intron_variant Intron 25 of 27 NP_000416.1 P32004-1
L1CAMNM_024003.3 linkc.3457+18C>A intron_variant Intron 25 of 26 NP_076493.1 P32004-2
L1CAMNM_001143963.2 linkc.3442+18C>A intron_variant Intron 24 of 25 NP_001137435.1 P32004-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
L1CAMENST00000370060.7 linkc.3457+18C>A intron_variant Intron 26 of 28 5 NM_001278116.2 ENSP00000359077.1 P32004-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.00000549
AC:
1
AN:
182254
Hom.:
0
AF XY:
0.0000149
AC XY:
1
AN XY:
67010
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000723
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.40
DANN
Benign
0.52

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.

Other links and lift over

dbSNP: rs76726076; hg19: chrX-153129320; API