3-295083-C-T

Variant names:

• chr3-295083-C-T
• rs331894
• NM_006614.4:c.-94-24600C>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.-94-24600C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,898 control chromosomes in the GnomAD database, including 26,929 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 0.56 (26929 hom., cov: 32)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-94-24600C>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.-94-24600C>T		intron_variant	Intron 2 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85468 AN: 151780 Hom.: 26872 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.563 AC: 85578 AN: 151898 Hom.: 26929 Cov.: 32 AF XY: 0.558 AC XY: 41412 AN XY: 74204

African (AFR) AF: 0.853 AC: 35391 AN: 41508

American (AMR) AF: 0.465 AC: 7086 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2176 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2570 AN: 5160

South Asian (SAS) AF: 0.688 AC: 3310 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3501 AN: 10484

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29869 AN: 67908

Other (OTH) AF: 0.560 AC: 1180 AN: 2106

Alfa AF: 0.483 Hom.: 9287

Bravo AF: 0.587

Asia WGS AF: 0.621 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.084
DANN	Benign	0.68
PhyloP100		-0.65
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: rs331894; hg19: chr3-336766;