rs2272524

Variant names:

• chr3-349318-G-A
• rs2272524
• NM_006614.4:c.849-41G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	NM_006614.4	MANE Select	c.849-41G>A		intron	N/A	NP_006605.2
	CHL1	NM_001253387.2		c.801-41G>A		intron	N/A	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.849-41G>A		intron	N/A	NP_001240317.1	A0A087X0M8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	ENST00000256509.7	TSL:1 MANE Select	c.849-41G>A		intron	N/A	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.801-41G>A		intron	N/A	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.849-41G>A		intron	N/A	ENSP00000483512.1	A0A087X0M8

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

GnomAD2 exomes AF: 0.292 AC: 55749 AN: 190764 AF XY: 0.300

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 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

African (AFR) AF: 0.0892 AC: 2672 AN: 29950

American (AMR) AF: 0.207 AC: 7654 AN: 36908

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7368 AN: 25204

East Asian (EAS) AF: 0.406 AC: 14802 AN: 36450

South Asian (SAS) AF: 0.357 AC: 28623 AN: 80256

European-Finnish (FIN) AF: 0.352 AC: 18031 AN: 51206

Middle Eastern (MID) AF: 0.211 AC: 1173 AN: 5570

European-Non Finnish (NFE) AF: 0.300 AC: 317430 AN: 1057766

Other (OTH) AF: 0.288 AC: 16532 AN: 57314

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

African (AFR) AF: 0.0996 AC: 4133 AN: 41502

American (AMR) AF: 0.219 AC: 3339 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 976 AN: 3464

East Asian (EAS) AF: 0.406 AC: 2097 AN: 5168

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4822

European-Finnish (FIN) AF: 0.346 AC: 3646 AN: 10532

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20489 AN: 67968

Other (OTH) AF: 0.249 AC: 526 AN: 2114

Alfa AF: 0.238 Hom.: 1263

Bravo AF: 0.228

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-1.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2272524;

hg19: chr3-391001;

COSMIC: COSV56589238;