3-270666-T-C

Variant names:

• chr3-270666-T-C
• rs6764363
• NM_006614.4:c.-95+25974T>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.-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
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006614.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	NM_006614.4	MANE Select	c.-95+25974T>C		intron	N/A	NP_006605.2
	CHL1	NM_001253387.2		c.-95+25974T>C		intron	N/A	NP_001240316.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	ENST00000256509.7	TSL:1 MANE Select	c.-95+25974T>C		intron	N/A	ENSP00000256509.2
	CHL1	ENST00000397491.6	TSL:1	c.-95+25974T>C		intron	N/A	ENSP00000380628.2
	CHL1	ENST00000435603.5	TSL:5	c.-94-49017T>C		intron	N/A	ENSP00000397445.1

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

African (AFR) AF: 0.366 AC: 15196 AN: 41498

American (AMR) AF: 0.292 AC: 4469 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3470

East Asian (EAS) AF: 0.105 AC: 547 AN: 5192

South Asian (SAS) AF: 0.349 AC: 1687 AN: 4828

European-Finnish (FIN) AF: 0.333 AC: 3517 AN: 10576

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24437 AN: 67994

Other (OTH) AF: 0.362 AC: 767 AN: 2116

Alfa AF: 0.355 Hom.: 30456

Bravo AF: 0.342

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		-0.22
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: rs6764363; hg19: chr3-312349;