3-314882-A-T

Variant names:

• chr3-314882-A-T
• rs392670
• NM_006614.4:c.-94-4801A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006614.4(CHL1):​c.-94-4801A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,930 control chromosomes in the GnomAD database, including 32,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (32232 hom., cov: 31)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-94-4801A>T		intron_variant	Intron 2 of 27	ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.-94-4801A>T		intron_variant	Intron 2 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94952 AN: 151812 Hom.: 32173 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95061 AN: 151930 Hom.: 32232 Cov.: 31 AF XY: 0.618 AC XY: 45908 AN XY: 74254

African (AFR) AF: 0.909 AC: 37724 AN: 41480

American (AMR) AF: 0.512 AC: 7812 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2531 AN: 5148

South Asian (SAS) AF: 0.680 AC: 3269 AN: 4810

European-Finnish (FIN) AF: 0.411 AC: 4335 AN: 10548

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.523 AC: 35554 AN: 67918

Other (OTH) AF: 0.633 AC: 1336 AN: 2110

Alfa AF: 0.370 Hom.: 818

Bravo AF: 0.642

Asia WGS AF: 0.632 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.80
DANN	Benign	0.67
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs392670; hg19: chr3-356565;