Variant 3-319825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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 criteria provided, single submitter B:1

Conservation

PhyloP100: -0.142

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 -14 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 id is 3058988.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4 linkuse as main transcript	c.49C>T	p.Leu17Phe	missense_variant	3/28	ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7 linkuse as main transcript	c.49C>T	p.Leu17Phe	missense_variant	3/28	1	NM_006614.4	P3	O00533-2

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

GnomAD3 exomes

AF:

0.254

AC:

62934

AN:

247384

Hom.:

9011

AF XY:

0.249

AC XY:

33323

AN XY:

133776

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 SAS exome

AF:

0.288

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

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.305

AC:

46305

AN:

151662

Hom.:

8431

Cov.:

AF XY:

0.305

AC XY:

22617

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.224

Hom.:

9662

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as 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

Benign

0.074

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

Cadd

Benign

0.11

Dann

Benign

0.12

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

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

MetaRNN

Benign

0.00020

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

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

1.0

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

REVEL

Benign

0.070

Sift

Benign

1.0

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

Sift4G

Benign

0.63

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

Polyphen

0.0

B;B;.;.;.;.;.

Vest4

0.050

MPC

0.012

ClinPred

0.0016

GERP RS

-2.0

Varity_R

0.026

gMVP

0.30

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