rs200638763

Variant names:

Variant summary

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

The NM_001278116.2(L1CAM):c.984C>T(p.Thr328Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,210,304 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 79 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 0.00029 ( 0 hom., 14 hem., cov: 24)

Exomes 𝑓: 0.00019 ( 0 hom. 65 hem. )

Consequence

L1CAM
NM_001278116.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.93

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=-0.8).

BP6

Variant X-153870063-G-A is Benign according to our data. Variant chrX-153870063-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153870063-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000293 (33/112521) while in subpopulation AMR AF= 0.0013 (14/10733). AF 95% confidence interval is 0.000788. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L1CAM	NM_001278116.2 link	c.984C>T	p.Thr328Thr	synonymous_variant	Exon 9 of 29	ENST00000370060.7	NP_001265045.1	P32004-1
L1CAM	NM_000425.5 link	c.984C>T	p.Thr328Thr	synonymous_variant	Exon 8 of 28		NP_000416.1	P32004-1
L1CAM	NM_024003.3 link	c.984C>T	p.Thr328Thr	synonymous_variant	Exon 8 of 27		NP_076493.1	P32004-2
L1CAM	NM_001143963.2 link	c.969C>T	p.Thr323Thr	synonymous_variant	Exon 7 of 26		NP_001137435.1	P32004-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
L1CAM	ENST00000370060.7 link	c.984C>T	p.Thr328Thr	synonymous_variant	Exon 9 of 29	5	NM_001278116.2	ENSP00000359077.1	P32004-1
L1CAM	ENST00000361699.8 link	c.984C>T	p.Thr328Thr	synonymous_variant	Exon 8 of 27	1		ENSP00000355380.4	P32004-2
L1CAM	ENST00000361981.7 link	c.969C>T	p.Thr323Thr	synonymous_variant	Exon 7 of 26	1		ENSP00000354712.3	P32004-3
L1CAM	ENST00000370055.5 link	c.969C>T	p.Thr323Thr	synonymous_variant	Exon 8 of 27	5		ENSP00000359072.1	P32004-3

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

112468

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

34626

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000244

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000372

AC:

AN:

182756

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

67384

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000251

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

204

AN:

1097783

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

363251

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.000310

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000298

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.000412

GnomAD4 genome

AF:

0.000293

AC:

AN:

112521

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

34689

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00130

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000244

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000310

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Feb 26, 2018

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Sep 28, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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

Sep 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely 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

-0.80

CADD

Benign

0.055

DANN

Benign

0.69

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.

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