X-153864670-C-T

Position:

chrX-153864670-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001278116.2(L1CAM):c.3081G>A(p.Ala1027Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,210,385 control chromosomes in the GnomAD database, including 5 homozygotes. There are 153 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 0.0025 ( 2 hom., 75 hem., cov: 24)

Exomes 𝑓: 0.00029 ( 3 hom. 78 hem. )

Consequence

L1CAM
NM_001278116.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.34

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-153864670-C-T is Benign according to our data. Variant chrX-153864670-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 92932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00255 (286/112342) while in subpopulation AFR AF= 0.00907 (281/30992). AF 95% confidence interval is 0.0082. There are 2 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L1CAM	NM_001278116.2 linkuse as main transcript	c.3081G>A	p.Ala1027Ala	synonymous_variant	24/29	ENST00000370060.7	NP_001265045.1	P32004-1
L1CAM	NM_000425.5 linkuse as main transcript	c.3081G>A	p.Ala1027Ala	synonymous_variant	23/28		NP_000416.1	P32004-1
L1CAM	NM_024003.3 linkuse as main transcript	c.3081G>A	p.Ala1027Ala	synonymous_variant	23/27		NP_076493.1	P32004-2
L1CAM	NM_001143963.2 linkuse as main transcript	c.3066G>A	p.Ala1022Ala	synonymous_variant	22/26		NP_001137435.1	P32004-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
L1CAM	ENST00000370060.7 linkuse as main transcript	c.3081G>A	p.Ala1027Ala	synonymous_variant	24/29	5	NM_001278116.2	ENSP00000359077.1	P32004-1
L1CAM	ENST00000361699.8 linkuse as main transcript	c.3081G>A	p.Ala1027Ala	synonymous_variant	23/27	1		ENSP00000355380.4	P32004-2
L1CAM	ENST00000361981.7 linkuse as main transcript	c.3066G>A	p.Ala1022Ala	synonymous_variant	22/26	1		ENSP00000354712.3	P32004-3
L1CAM	ENST00000370055.5 linkuse as main transcript	c.3066G>A	p.Ala1022Ala	synonymous_variant	23/27	5		ENSP00000359072.1	P32004-3

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

286

AN:

112290

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

AN XY:

34458

show subpopulations

Gnomad AFR

AF:

0.00909

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.0000188

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000790

AC:

145

AN:

183449

Hom.:

AF XY:

0.000560

AC XY:

AN XY:

67883

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.000146

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:

0.0000244

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000292

AC:

321

AN:

1098043

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

363413

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000238

Gnomad4 OTH exome

AF:

0.000607

GnomAD4 genome

AF:

0.00255

AC:

286

AN:

112342

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

AN XY:

34520

show subpopulations

Gnomad4 AFR

AF:

0.00907

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.0000870

Hom.:

Bravo

AF:

0.00331

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 26, 2012

- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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