rs62230378

Variant names:

• chr3-382221-A-G
• rs62230378
• NM_006614.4:c.1919A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006614.4(CHL1):​c.1919A>G​(p.Gln640Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0255 in 1,613,620 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (37 hom., cov: 32)
  • Exomes 𝑓: 0.026 (631 hom.)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 10 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-AS1 (HGNC:40148): (CHL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052048266).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.019 (2889/152326) while in subpopulation NFE AF = 0.0291 (1981/68022). AF 95% confidence interval is 0.0281. There are 37 homozygotes in GnomAd4. There are 1354 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2889 AD gene.

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.1919A>G	p.Gln640Arg	missense	Exon 17 of 28	NP_006605.2
	CHL1	NM_001253387.2		c.1871A>G	p.Gln624Arg	missense	Exon 16 of 27	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.1919A>G	p.Gln640Arg	missense	Exon 15 of 25	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.1919A>G	p.Gln640Arg	missense	Exon 17 of 28	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.1871A>G	p.Gln624Arg	missense	Exon 16 of 27	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.1919A>G	p.Gln640Arg	missense	Exon 15 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2889 AN: 152208 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00576

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.0179 AC: 4493 AN: 251084 AF XY: 0.0179

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.00517

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0199

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0262 AC: 38261 AN: 1461294 Hom.: 631 Cov.: 31 AF XY: 0.0252 AC XY: 18293 AN XY: 726958

African (AFR) AF: 0.00458 AC: 153 AN: 33438

American (AMR) AF: 0.0140 AC: 626 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00555 AC: 145 AN: 26116

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39686

South Asian (SAS) AF: 0.00408 AC: 352 AN: 86212

European-Finnish (FIN) AF: 0.0203 AC: 1084 AN: 53406

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.0311 AC: 34544 AN: 1111618

Other (OTH) AF: 0.0222 AC: 1339 AN: 60370

GnomAD4 genome AF: 0.0190 AC: 2889 AN: 152326 Hom.: 37 Cov.: 32 AF XY: 0.0182 AC XY: 1354 AN XY: 74484

African (AFR) AF: 0.00575 AC: 239 AN: 41590

American (AMR) AF: 0.0226 AC: 346 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.0223 AC: 237 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1981 AN: 68022

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0249 Hom.: 194

Bravo AF: 0.0183

TwinsUK AF: 0.0318 AC: 118

ALSPAC AF: 0.0324 AC: 125

ESP6500AA AF: 0.00567 AC: 25

ESP6500EA AF: 0.0243 AC: 209

ExAC AF: 0.0172 AC: 2089

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0258

EpiControl AF: 0.0251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.053
Sift	Benign	0.65	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.088
MPC		0.012
ClinPred		0.011	T
GERP RS		4.0
Varity_R		0.097
gMVP		0.39
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62230378; hg19: chr3-423904;