rs11917787

Variant names:

• chr3-212236-A-G
• rs11917787
• NM_006614.4:c.-175+15173A>G

Variant summary

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

The ENST00000256509.7(CHL1):​c.-175+15173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,092 control chromosomes in the GnomAD database, including 1,564 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 0.13 (1564 hom., cov: 31)
• Consequence: CHL1 ENST00000256509.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000256509.7. 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.-175+15173A>G		intron	N/A	NP_006605.2
	CHL1	NM_001253387.2		c.-175+15173A>G		intron	N/A	NP_001240316.1
	CHL1	NR_045572.2		n.204+14144A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	ENST00000256509.7	TSL:1 MANE Select	c.-175+15173A>G		intron	N/A	ENSP00000256509.2
	CHL1	ENST00000397491.6	TSL:1	c.-175+15173A>G		intron	N/A	ENSP00000380628.2
	CHL1	ENST00000435603.5	TSL:5	c.-95+14144A>G		intron	N/A	ENSP00000397445.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19384 AN: 151972 Hom.: 1561 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.128 AC: 19400 AN: 152092 Hom.: 1564 Cov.: 31 AF XY: 0.133 AC XY: 9925 AN XY: 74346

African (AFR) AF: 0.117 AC: 4874 AN: 41484

American (AMR) AF: 0.142 AC: 2164 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2043 AN: 5154

South Asian (SAS) AF: 0.286 AC: 1380 AN: 4824

European-Finnish (FIN) AF: 0.149 AC: 1575 AN: 10576

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0973 AC: 6616 AN: 67990

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.113 Hom.: 126

Bravo AF: 0.128

Asia WGS AF: 0.347 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.064
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: rs11917787; hg19: chr3-253919;