3-298757-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006614.4(CHL1):c.-94-20926T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,040 control chromosomes in the GnomAD database, including 27,837 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 0.57 (27837 hom., cov: 31)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.82

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4	c.-94-20926T>C		intron_variant		ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.-94-20926T>C		intron_variant		1	NM_006614.4	P3

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86992 AN: 151922 Hom.: 27784 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.573 AC: 87099 AN: 152040 Hom.: 27837 Cov.: 31 AF XY: 0.569 AC XY: 42280 AN XY: 74324

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.572

Alfa AF: 0.463 Hom.: 15676

Bravo AF: 0.595

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.12
Dann	Benign	0.72

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: rs332479; hg19: chr3-340440;