3-355870-A-G

Variant names:

• chr3-355870-A-G
• rs892295
• NM_006614.4:c.1165+1099A>G

Variant summary

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

The NM_006614.4(CHL1):​c.1165+1099A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,142 control chromosomes in the GnomAD database, including 61,264 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 0.88 (61264 hom., cov: 32)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

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.1165+1099A>G		intron	N/A	NP_006605.2
	CHL1	NM_001253387.2		c.1117+1099A>G		intron	N/A	NP_001240316.1
	CHL1	NM_001253388.1		c.1165+1099A>G		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.1165+1099A>G		intron	N/A	ENSP00000256509.2
	CHL1	ENST00000397491.6	TSL:1	c.1117+1099A>G		intron	N/A	ENSP00000380628.2
	CHL1	ENST00000620033.4	TSL:1	c.1165+1099A>G		intron	N/A	ENSP00000483512.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133809 AN: 152024 Hom.: 61245 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.976

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.880 AC: 133867 AN: 152142 Hom.: 61264 Cov.: 32 AF XY: 0.883 AC XY: 65679 AN XY: 74382

African (AFR) AF: 0.595 AC: 24654 AN: 41410

American (AMR) AF: 0.949 AC: 14515 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3454 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5144 AN: 5174

South Asian (SAS) AF: 0.976 AC: 4712 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67644 AN: 68034

Other (OTH) AF: 0.917 AC: 1939 AN: 2114

Alfa AF: 0.864 Hom.: 32082

Bravo AF: 0.864

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		-0.081
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: rs892295; hg19: chr3-397553;