3-326074-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960

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]

ACMG classification

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	UniProt
CHL1	NM_006614.4	c.197+10G>C		intron_variant		ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.197+10G>C		intron_variant		1	NM_006614.4	P3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52653 AN: 151724 Hom.: 14381 Cov.: 32

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

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.: 23 AF XY: 0.210 AC XY: 147292 AN XY: 701592

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.: 32 AF XY: 0.336 AC XY: 24971 AN XY: 74210

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHL1-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2022

- -

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

Other links and lift over

dbSNP: rs162734; hg19: chr3-367757;