chr3-227352-C-T

Variant names:

• chr3-227352-C-T
• rs2055314
• NM_006614.4:c.-174-17261C>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.-174-17261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,104 control chromosomes in the GnomAD database, including 15,502 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 0.41 (15502 hom., cov: 33)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-174-17261C>T		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.-174-17261C>T		intron_variant	Intron 1 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61960 AN: 151986 Hom.: 15498 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.407 AC: 61970 AN: 152104 Hom.: 15502 Cov.: 33 AF XY: 0.411 AC XY: 30555 AN XY: 74350

African (AFR) AF: 0.112 AC: 4667 AN: 41530

American (AMR) AF: 0.515 AC: 7868 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3466

East Asian (EAS) AF: 0.511 AC: 2634 AN: 5156

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4814

European-Finnish (FIN) AF: 0.580 AC: 6135 AN: 10574

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36483 AN: 67962

Other (OTH) AF: 0.403 AC: 851 AN: 2114

Alfa AF: 0.468 Hom.: 9846

Bravo AF: 0.390

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.18
PhyloP100		-2.0
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: rs2055314; hg19: chr3-269035;