Genetic Variant CHL1:p.Tyr52Cys (chr3-326022-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006614.4(CHL1):c.155A>G(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,611,668 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044495493).

BP6

Variant 3-326022-A-G is Benign according to our data. Variant chr3-326022-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3034045.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4 link	c.155A>G	p.Tyr52Cys	missense_variant	Exon 4 of 28	ENST00000256509.7	NP_006605.2	O00533-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7 link	c.155A>G	p.Tyr52Cys	missense_variant	Exon 4 of 28	1	NM_006614.4	ENSP00000256509.2		O00533-2

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00115

AC:

288

AN:

249950

Hom.:

AF XY:

0.00109

AC XY:

147

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000353

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00175

AC:

2555

AN:

1459506

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00196

GnomAD4 genome

AF:

0.00121

AC:

184

AN:

152162

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00225

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00136

AC:

165

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00208

EpiControl

AF:

0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHL1-related disorder

Benign:1

Feb 21, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;T;.;.;.;T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.044

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.53

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

N;N;N;N;N;N;.

REVEL

Uncertain

0.41

Sift

Benign

0.17

T;T;T;T;T;T;.

Sift4G

Benign

0.18

T;T;D;D;T;D;T

Polyphen

0.82

P;P;.;.;.;.;.

Vest4

0.49

MVP

0.79

MPC

0.040

ClinPred

0.031

GERP RS

5.7

Varity_R

0.14

gMVP

0.76

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

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