chr3-298757-T-C

Variant names:

• chr3-298757-T-C
• rs332479
• NM_006614.4:c.-94-20926T>C

Variant summary

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

The NM_006614.4(CHL1):​c.-94-20926T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,040 control chromosomes in the GnomAD database, including 27,837 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 0.57 (27837 hom., cov: 31)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.82
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-94-20926T>C		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.-94-20926T>C		intron_variant	Intron 2 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86992 AN: 151922 Hom.: 27784 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.573 AC: 87099 AN: 152040 Hom.: 27837 Cov.: 31 AF XY: 0.569 AC XY: 42280 AN XY: 74324

African (AFR) AF: 0.866 AC: 35941 AN: 41488

American (AMR) AF: 0.472 AC: 7212 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2167 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2620 AN: 5170

South Asian (SAS) AF: 0.716 AC: 3453 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3841 AN: 10576

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30158 AN: 67930

Other (OTH) AF: 0.572 AC: 1209 AN: 2112

Alfa AF: 0.484 Hom.: 23109

Bravo AF: 0.595

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.72
PhyloP100		-4.8
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: rs332479; hg19: chr3-340440;