NM_006614.4:c.-175+2826A>C

Variant names:

• chr3-199889-A-C
• rs17329226
• NM_006614.4:c.-175+2826A>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.-175+2826A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,034 control chromosomes in the GnomAD database, including 11,778 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 0.38 (11778 hom., cov: 33)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-175+2826A>C		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.-175+2826A>C		intron_variant	Intron 1 of 27	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57197 AN: 151916 Hom.: 11772 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.376 AC: 57231 AN: 152034 Hom.: 11778 Cov.: 33 AF XY: 0.367 AC XY: 27270 AN XY: 74324

African (AFR) AF: 0.509 AC: 21077 AN: 41442

American (AMR) AF: 0.310 AC: 4746 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3466

East Asian (EAS) AF: 0.0280 AC: 145 AN: 5184

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3056 AN: 10570

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24086 AN: 67948

Other (OTH) AF: 0.377 AC: 795 AN: 2106

Alfa AF: 0.367 Hom.: 17610

Bravo AF: 0.382

Asia WGS AF: 0.164 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		0.41
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: rs17329226; hg19: chr3-241572;