Genetic Variant NM_001278116.2:c.-109+95_-109+96insGCCG (chrX-153885969-G-GCGGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001278116.2(L1CAM):c.-109+95_-109+96insGCCG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 1.0 ( 38620 hom., 31069 hem., cov: 0)

Exomes 𝑓: 1.0 ( 235878 hom. 201392 hem. )

Failed GnomAD Quality Control

Consequence

L1CAM
NM_001278116.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.532

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:

ENSG00000284987 (HGNC:):

ENSG00000284987 links:

L1CAM-AS1 (HGNC:55247): (L1CAM antisense RNA 1)

L1CAM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-153885969-G-GCGGC is Benign according to our data. Variant chrX-153885969-G-GCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 804117.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L1CAM	NM_001278116.2 link	c.-109+95_-109+96insGCCG		intron_variant	Intron 1 of 28	ENST00000370060.7	NP_001265045.1	P32004-1
L1CAM-AS1	NR_130768.1 link	n.795_796insCGGC		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L1CAM	ENST00000370060.7 link	c.-109+95_-109+96insGCCG		intron_variant	Intron 1 of 28	5	NM_001278116.2	ENSP00000359077.1		P32004-1
ENSG00000284987	ENST00000646191.1 link	n.97-10026_97-10025insGCCG		intron_variant	Intron 1 of 4			ENSP00000493873.1		A0A2R8Y4P6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

108280

AN:

108286

Hom.:

38625

Cov.:

AF XY:

1.00

AC XY:

31026

AN XY:

31028

FAILED QC

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

Gnomad AMR exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

673197

AN:

673250

Hom.:

235878

Cov.:

AF XY:

1.00

AC XY:

201392

AN XY:

201396

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

1.00

AC:

108313

AN:

108319

Hom.:

38620

Cov.:

AF XY:

1.00

AC XY:

31069

AN XY:

31071

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

0.986

Hom.:

8351

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked hydrocephalus syndrome

Benign:1

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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