chrX-153862280-G-A

Position:

• chrX-153862280-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0990

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
L1CAM	NM_001278116.2	c.*383C>T		3_prime_UTR_variant	29/29	ENST00000370060.7
L1CAM	NM_000425.5	c.*383C>T		3_prime_UTR_variant	28/28
L1CAM	NM_001143963.2	c.*383C>T		3_prime_UTR_variant	26/26
L1CAM	NM_024003.3	c.*383C>T		3_prime_UTR_variant	27/27

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 4691 AN: 111414 Hom.: 101 Cov.: 23 AF XY: 0.0367 AC XY: 1234 AN XY: 33640

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.: 85 Cov.: 0 AF XY: 0.0552 AC XY: 679 AN XY: 12295

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.: 23 AF XY: 0.0366 AC XY: 1234 AN XY: 33700

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

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

Other links and lift over

dbSNP: rs41311708; hg19: chrX-153127735;