rs2272524

Positions:

• chr3-349318-G-A
• chr3-349318-G-C
• chr3-349318-G-T

Variant summary

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

The NM_006614.4(CHL1):​c.849-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,532,660 control chromosomes in the GnomAD database, including 69,392 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 0.25 (5300 hom., cov: 34)
  • Exomes 𝑓: 0.30 (64092 hom.)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4	c.849-41G>A		intron_variant		ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.849-41G>A		intron_variant		1	NM_006614.4	P3
CHL1	ENST00000397491.6	c.801-41G>A		intron_variant		1
CHL1	ENST00000620033.4	c.849-41G>A		intron_variant		1		A1
CHL1	ENST00000453040.5	c.*1139-41G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37294 AN: 151918 Hom.: 5307 Cov.: 34

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.249

GnomAD3 exomes AF: 0.292 AC: 55749 AN: 190764 Hom.: 8602 AF XY: 0.300 AC XY: 31022 AN XY: 103366

Gnomad AFR exome AF: 0.0922

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.298

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.300 AC: 414285 AN: 1380624 Hom.: 64092 Cov.: 23 AF XY: 0.302 AC XY: 207636 AN XY: 687034

Gnomad4 AFR exome AF: 0.0892

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.245 AC: 37284 AN: 152036 Hom.: 5300 Cov.: 34 AF XY: 0.248 AC XY: 18428 AN XY: 74304

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.249

Alfa AF: 0.240 Hom.: 1258

Bravo AF: 0.228

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
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: rs2272524; hg19: chr3-391001; COSMIC: COSV56589238;