rs62230378

chr3-382221-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4	c.1919A>G	p.Gln640Arg	missense_variant	17/28	ENST00000256509.7
CHL1-AS1	NR_110739.1	n.259+346T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.1919A>G	p.Gln640Arg	missense_variant	17/28	1	NM_006614.4	P3
CHL1-AS1	ENST00000417612.1	n.259+346T>C		intron_variant, non_coding_transcript_variant		1

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

GnomAD3 exomes AF: 0.0179 AC: 4493 AN: 251084 Hom.: 57 AF XY: 0.0179 AC XY: 2431 AN XY: 135668

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 SAS exome AF: 0.00373

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

Gnomad4 AFR exome AF: 0.00458

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.00555

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0222

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

Gnomad4 AFR AF: 0.00575

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0253 Hom.: 89

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 v4.3

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
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T;T;T
MetaRNN	Benign	0.0052	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.32	N;N;.
REVEL	Benign	0.053
Sift	Benign	0.65	T;T;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.088
MPC		0.012
ClinPred		0.011	T
GERP RS		4.0
Varity_R		0.097
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs62230378; hg19: chr3-423904;