dbSNP rs372673845: CHL1:p.Gly603Asp (chr3-377874-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006614.4(CHL1):c.1808G>A(p.Gly603Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G603A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.94

Publications

0 publications found

Variant links:

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

CHL1 links:

CHL1-AS1 (HGNC:40148): (CHL1 antisense RNA 1)

CHL1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006614.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHL1	NM_006614.4	MANE Select	c.1808G>A	p.Gly603Asp	missense	Exon 16 of 28	NP_006605.2
CHL1	NM_001253387.2		c.1760G>A	p.Gly587Asp	missense	Exon 15 of 27	NP_001240316.1	O00533-1
CHL1	NM_001253388.1		c.1808G>A	p.Gly603Asp	missense	Exon 14 of 25	NP_001240317.1	A0A087X0M8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHL1	ENST00000256509.7	TSL:1 MANE Select	c.1808G>A	p.Gly603Asp	missense	Exon 16 of 28	ENSP00000256509.2	O00533-2
CHL1	ENST00000397491.6	TSL:1	c.1760G>A	p.Gly587Asp	missense	Exon 15 of 27	ENSP00000380628.2	O00533-1
CHL1	ENST00000620033.4	TSL:1	c.1808G>A	p.Gly603Asp	missense	Exon 14 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110210

Other (OTH)

AF:

0.00

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.0

PhyloP100

4.9

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.83

MutPred

0.93

Loss of catalytic residue at D585 (P = 0.1307)

MVP

0.85

MPC

0.082

ClinPred

1.0

GERP RS

5.7

Varity_R

0.94

gMVP

0.86

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over