rs6764363

Positions:

• chr3-270666-T-C
• chr3-270666-T-G

Variant summary

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

The NM_006614.4(CHL1):​c.-95+25974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,174 control chromosomes in the GnomAD database, including 9,258 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 0.34 (9258 hom., cov: 33)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-95+25974T>C		intron_variant		ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.-95+25974T>C		intron_variant		1	NM_006614.4	ENSP00000256509	P3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52291 AN: 152056 Hom.: 9246 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.344 AC: 52345 AN: 152174 Hom.: 9258 Cov.: 33 AF XY: 0.340 AC XY: 25286 AN XY: 74396

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.362

Alfa AF: 0.355 Hom.: 21521

Bravo AF: 0.342

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.71

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: rs6764363; hg19: chr3-312349;