rs17329226

Positions:

• chr3-199889-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHL1	NM_006614.4	c.-175+2826A>C		intron_variant		ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.-175+2826A>C		intron_variant		1	NM_006614.4	P3

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.377

Alfa AF: 0.363 Hom.: 13636

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17329226; hg19: chr3-241572;