chrX-153862460-C-G

Position:

• chrX-153862460-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001278116.2(L1CAM):​c.*203G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 382,774 control chromosomes in the GnomAD database, including 43 homozygotes. There are 570 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 0.014 (33 hom., 412 hem., cov: 23)
  • Exomes 𝑓: 0.0021 (10 hom. 158 hem.)
• Consequence: L1CAM NM_001278116.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-153862460-C-G is Benign according to our data. Variant chrX-153862460-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (1526/112605) while in subpopulation AFR AF= 0.0464 (1441/31060). AF 95% confidence interval is 0.0444. There are 33 homozygotes in gnomad4. There are 412 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L1CAM	NM_001278116.2	c.*203G>C		3_prime_UTR_variant	29/29	ENST00000370060.7
L1CAM	NM_000425.5	c.*203G>C		3_prime_UTR_variant	28/28
L1CAM	NM_001143963.2	c.*203G>C		3_prime_UTR_variant	26/26
L1CAM	NM_024003.3	c.*203G>C		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L1CAM	ENST00000370060.7	c.*203G>C		3_prime_UTR_variant	29/29	5	NM_001278116.2	A1
L1CAM	ENST00000361981.7	c.*203G>C		3_prime_UTR_variant	26/26	1		A1
L1CAM	ENST00000370055.5	c.*203G>C		3_prime_UTR_variant	27/27	5		A1
L1CAM	ENST00000370058.7	c.*203G>C		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 1523 AN: 112554 Hom.: 33 Cov.: 23 AF XY: 0.0119 AC XY: 412 AN XY: 34716

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.00859

GnomAD4 exome AF: 0.00210 AC: 567 AN: 270169 Hom.: 10 Cov.: 3 AF XY: 0.00192 AC XY: 158 AN XY: 82173

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000214

Gnomad4 OTH exome AF: 0.00540

GnomAD4 genome AF: 0.0136 AC: 1526 AN: 112605 Hom.: 33 Cov.: 23 AF XY: 0.0118 AC XY: 412 AN XY: 34777

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000263

Gnomad4 OTH AF: 0.00849

Alfa AF: 0.00947 Hom.: 28

Bravo AF: 0.0157

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.47

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: rs150098621; hg19: chrX-153127915;