NM_006614.4:c.385+1123G>C

Variant names:

• chr3-329477-G-C
• rs330891
• NM_006614.4:c.385+1123G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006614.4(CHL1):​c.385+1123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006614.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	NM_006614.4	MANE Select	c.385+1123G>C		intron	N/A	NP_006605.2
	CHL1	NM_001253387.2		c.385+1123G>C		intron	N/A	NP_001240316.1
	CHL1	NM_001253388.1		c.385+1123G>C		intron	N/A	NP_001240317.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	ENST00000256509.7	TSL:1 MANE Select	c.385+1123G>C		intron	N/A	ENSP00000256509.2
	CHL1	ENST00000397491.6	TSL:1	c.385+1123G>C		intron	N/A	ENSP00000380628.2
	CHL1	ENST00000620033.4	TSL:1	c.385+1123G>C		intron	N/A	ENSP00000483512.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.26
PhyloP100		-0.59

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: rs330891; hg19: chr3-371160;