rs781854219

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001278116.2(L1CAM):c.3739A>G(p.Thr1247Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,338 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000046 ( 0 hom. 0 hem. )

Consequence

L1CAM
NM_001278116.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.887

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

L1 syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp
MASA syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
X-linked complicated corpus callosum dysgenesis
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
X-linked complicated spastic paraplegia type 1
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

L1CAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06974539).

BP6

Variant X-153862698-T-C is Benign according to our data. Variant chrX-153862698-T-C is described in ClinVar as Benign. ClinVar VariationId is 2730309.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
L1CAM	NM_001278116.2	MANE Select	c.3739A>G	p.Thr1247Ala	missense	Exon 29 of 29	NP_001265045.1	P32004-1
L1CAM	NM_000425.5		c.3739A>G	p.Thr1247Ala	missense	Exon 28 of 28	NP_000416.1	P32004-1
L1CAM	NM_024003.3		c.3727A>G	p.Thr1243Ala	missense	Exon 27 of 27	NP_076493.1	P32004-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
L1CAM	ENST00000370060.7	TSL:5 MANE Select	c.3739A>G	p.Thr1247Ala	missense	Exon 29 of 29	ENSP00000359077.1	P32004-1
L1CAM	ENST00000361699.8	TSL:1	c.3727A>G	p.Thr1243Ala	missense	Exon 27 of 27	ENSP00000355380.4	P32004-2
L1CAM	ENST00000361981.7	TSL:1	c.3712A>G	p.Thr1238Ala	missense	Exon 26 of 26	ENSP00000354712.3	P32004-3

Frequencies

GnomAD3 genomes

AF:

0.00000886

AC:

AN:

112824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

181493

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000433

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26389

American (AMR)

AF:

0.00

AC:

AN:

35178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19356

East Asian (EAS)

AF:

0.000166

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

54067

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841621

Other (OTH)

AF:

0.00

AC:

AN:

46057

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000886

AC:

AN:

112824

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31078

American (AMR)

AF:

0.00

AC:

AN:

10765

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.000281

AC:

AN:

3559

South Asian (SAS)

AF:

0.00

AC:

AN:

2803

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53247

Other (OTH)

AF:

0.00

AC:

AN:

1519

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.47

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.78

M_CAP

Benign

0.035

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

PhyloP100

0.89

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.023

Sift

Benign

0.37

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.027

MutPred

0.11

Loss of glycosylation at T1247 (P = 0.0032)

MVP

0.71

MPC

0.53

ClinPred

0.024

GERP RS

2.4

Varity_R

0.058

gMVP

0.48

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over