Variant 3-326074-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006614.4(CHL1):c.197+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,555,454 control chromosomes in the GnomAD database, including 52,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14431 hom., cov: 32)

Exomes 𝑓: 0.21 ( 38541 hom. )

Consequence

CHL1
NM_006614.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0960

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-326074-G-C is Benign according to our data. Variant chr3-326074-G-C is described in ClinVar as [Benign]. Clinvar id is 1676925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4 linkuse as main transcript	c.197+10G>C		intron_variant		ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7 linkuse as main transcript	c.197+10G>C		intron_variant		1	NM_006614.4	ENSP00000256509	P3	O00533-2

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52653

AN:

151724

Hom.:

14381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.00948

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.309

GnomAD3 exomes

AF:

0.209

AC:

51471

AN:

246746

Hom.:

8634

AF XY:

0.202

AC XY:

26985

AN XY:

133508

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.00557

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.212

AC:

298008

AN:

1403612

Hom.:

38541

Cov.:

AF XY:

0.210

AC XY:

147292

AN XY:

701592

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.0118

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.225

GnomAD4 genome

AF:

0.347

AC:

52760

AN:

151842

Hom.:

14431

Cov.:

AF XY:

0.336

AC XY:

24971

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.762

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.00931

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.246

Hom.:

1180

Bravo

AF:

0.367

Asia WGS

AF:

0.134

AC:

470

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CHL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

DANN

Benign

0.40

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