rs145717130

chrX-153866710-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001278116.2(L1CAM):c.2370C>T(p.Ala790=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,209,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000036 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000014 (0 hom. 2 hem.)
• Consequence: L1CAM NM_001278116.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.20

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-153866710-G-A is Benign according to our data. Variant chrX-153866710-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 412597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L1CAM	NM_001278116.2	c.2370C>T	p.Ala790=	synonymous_variant	19/29	ENST00000370060.7
L1CAM	NM_000425.5	c.2370C>T	p.Ala790=	synonymous_variant	18/28
L1CAM	NM_024003.3	c.2370C>T	p.Ala790=	synonymous_variant	18/27
L1CAM	NM_001143963.2	c.2355C>T	p.Ala785=	synonymous_variant	17/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L1CAM	ENST00000370060.7	c.2370C>T	p.Ala790=	synonymous_variant	19/29	5	NM_001278116.2	A1
L1CAM	ENST00000361699.8	c.2370C>T	p.Ala790=	synonymous_variant	18/27	1		P4
L1CAM	ENST00000361981.7	c.2355C>T	p.Ala785=	synonymous_variant	17/26	1		A1
L1CAM	ENST00000370055.5	c.2355C>T	p.Ala785=	synonymous_variant	18/27	5		A1

Frequencies

GnomAD3 genomes AF: 0.0000359 AC: 4 AN: 111520 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33712

Gnomad AFR AF: 0.0000978

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000327 AC: 6 AN: 183299 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.000441

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1097955 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2 AN XY: 363311

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000852

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome AF: 0.0000359 AC: 4 AN: 111574 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33776

Gnomad4 AFR AF: 0.0000976

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	2.1
Dann	Benign	0.54

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: rs145717130; hg19: chrX-153132165; COSMIC: COSV100648892; COSMIC: COSV100648892;