rs2272522

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006614.4(CHL1):c.49C>T(p.Leu17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,599,498 control chromosomes in the GnomAD database, including 47,599 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.31 ( 8431 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39168 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.142

Publications

42 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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
partial deletion of the short arm of chromosome 3
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CHL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.027452E-4).

BP6

Variant 3-319825-C-T is Benign according to our data. Variant chr3-319825-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058988.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

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.49C>T	p.Leu17Phe	missense	Exon 3 of 28	NP_006605.2
CHL1	NM_001253387.2		c.49C>T	p.Leu17Phe	missense	Exon 3 of 27	NP_001240316.1	O00533-1
CHL1	NM_001253388.1		c.49C>T	p.Leu17Phe	missense	Exon 1 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.49C>T	p.Leu17Phe	missense	Exon 3 of 28	ENSP00000256509.2	O00533-2
CHL1	ENST00000397491.6	TSL:1	c.49C>T	p.Leu17Phe	missense	Exon 3 of 27	ENSP00000380628.2	O00533-1
CHL1	ENST00000620033.4	TSL:1	c.49C>T	p.Leu17Phe	missense	Exon 1 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46229

AN:

151544

Hom.:

8409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.254

AC:

62934

AN:

247384

AF XY:

0.249

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.223

AC:

323554

AN:

1447836

Hom.:

39168

Cov.:

AF XY:

0.223

AC XY:

160990

AN XY:

720480

show subpopulations

African (AFR)

AF:

0.526

AC:

17305

AN:

32884

American (AMR)

AF:

0.259

AC:

11428

AN:

44102

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5598

AN:

25878

East Asian (EAS)

AF:

0.316

AC:

12466

AN:

39396

South Asian (SAS)

AF:

0.282

AC:

24059

AN:

85322

European-Finnish (FIN)

AF:

0.238

AC:

12538

AN:

52766

Middle Eastern (MID)

AF:

0.187

AC:

1069

AN:

5718

European-Non Finnish (NFE)

AF:

0.204

AC:

224711

AN:

1102034

Other (OTH)

AF:

0.241

AC:

14380

AN:

59736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

10907

21814

32720

43627

54534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8058

16116

24174

32232

40290

<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:

0.305

AC:

46305

AN:

151662

Hom.:

8431

Cov.:

AF XY:

0.305

AC XY:

22617

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.512

AC:

21214

AN:

41414

American (AMR)

AF:

0.251

AC:

3806

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

783

AN:

3464

East Asian (EAS)

AF:

0.332

AC:

1701

AN:

5118

South Asian (SAS)

AF:

0.299

AC:

1438

AN:

4814

European-Finnish (FIN)

AF:

0.237

AC:

2494

AN:

10520

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.208

AC:

14082

AN:

67836

Other (OTH)

AF:

0.279

AC:

588

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1513

3027

4540

6054

7567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.234

Hom.:

19632

Bravo

AF:

0.316

TwinsUK

AF:

0.217

AC:

806

ALSPAC

AF:

0.198

AC:

765

ESP6500AA

AF:

0.517

AC:

2278

ESP6500EA

AF:

0.202

AC:

1740

ExAC

AF:

0.260

AC:

31545

Asia WGS

AF:

0.326

AC:

1134

AN:

3476

EpiCase

AF:

0.201

EpiControl

AF:

0.205

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CHL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.11

(source)

DANN

Benign

0.12

DEOGEN2

Benign

0.040

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

MetaRNN

Benign

0.00020

MetaSVM

Benign

-0.98

PhyloP100

-0.14

PrimateAI

Benign

0.26

PROVEAN

Benign

1.0

REVEL

Benign

0.070

Sift

Benign

1.0

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.050

MPC

0.012

ClinPred

0.0016

GERP RS

-2.0

PromoterAI

0.015

Neutral

(source)

Varity_R

0.026

gMVP

0.30

Mutation Taster

=97/3

polymorphism (auto)

(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

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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