Variant X-153862280-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278116.2(L1CAM):c.*383C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 172,551 control chromosomes in the GnomAD database, including 186 homozygotes. There are 1,913 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 0.042 ( 101 hom., 1234 hem., cov: 23)

Exomes 𝑓: 0.052 ( 85 hom. 679 hem. )

Consequence

L1CAM
NM_001278116.2 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0990

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-153862280-G-A is Benign according to our data. Variant chrX-153862280-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1344425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
L1CAM	NM_001278116.2 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	29/29	ENST00000370060.7
L1CAM	NM_000425.5 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	28/28
L1CAM	NM_001143963.2 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	26/26
L1CAM	NM_024003.3 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L1CAM	ENST00000370060.7 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	29/29	5	NM_001278116.2	A1	P32004-1
L1CAM	ENST00000361981.7 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	26/26	1		A1	P32004-3
L1CAM	ENST00000370055.5 linkuse as main transcript	c.*383C>T	3_prime_UTR_variant	27/27	5		A1	P32004-3

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

4691

AN:

111414

Hom.:

101

Cov.:

AF XY:

0.0367

AC XY:

1234

AN XY:

33640

show subpopulations

Gnomad AFR

AF:

0.00958

Gnomad AMI

AF:

0.0265

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00412

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.0430

GnomAD4 exome

AF:

0.0521

AC:

3180

AN:

61087

Hom.:

Cov.:

AF XY:

0.0552

AC XY:

679

AN XY:

12295

show subpopulations

Gnomad4 AFR exome

AF:

0.00717

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.0396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00542

Gnomad4 FIN exome

AF:

0.0570

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.0475

GnomAD4 genome

AF:

0.0421

AC:

4692

AN:

111464

Hom.:

101

Cov.:

AF XY:

0.0366

AC XY:

1234

AN XY:

33700

show subpopulations

Gnomad4 AFR

AF:

0.00956

Gnomad4 AMR

AF:

0.0341

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0670

Gnomad4 OTH

AF:

0.0424

Alfa

AF:

0.0536

Hom.:

289

Bravo

AF:

0.0408

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 03, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

DANN

Benign

0.42

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