3-239304-C-A

Variant names:

• chr3-239304-C-A
• rs4003413
• NM_006614.4:c.-174-5309C>A

Variant summary

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

The NM_006614.4(CHL1):​c.-174-5309C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,012 control chromosomes in the GnomAD database, including 21,266 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 0.51 (21266 hom., cov: 32)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-174-5309C>A		intron_variant	Intron 1 of 27	ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.-174-5309C>A		intron_variant	Intron 1 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77170 AN: 151894 Hom.: 21260 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.508 AC: 77194 AN: 152012 Hom.: 21266 Cov.: 32 AF XY: 0.508 AC XY: 37723 AN XY: 74310

African (AFR) AF: 0.291 AC: 12052 AN: 41460

American (AMR) AF: 0.583 AC: 8896 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1684 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2698 AN: 5164

South Asian (SAS) AF: 0.344 AC: 1659 AN: 4822

European-Finnish (FIN) AF: 0.627 AC: 6633 AN: 10578

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41842 AN: 67938

Other (OTH) AF: 0.497 AC: 1048 AN: 2108

Alfa AF: 0.556 Hom.: 10978

Bravo AF: 0.497

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-1.1
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: rs4003413; hg19: chr3-280987;