3-377918-G-T

Variant names:

• chr3-377918-G-T
• rs186218301
• NM_006614.4:c.1852G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006614.4(CHL1):​c.1852G>T​(p.Asp618Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D618N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• 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-AS1 (HGNC:40148): (CHL1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1852G>T	p.Asp618Tyr	missense	Exon 16 of 28	NP_006605.2
	CHL1	NM_001253387.2		c.1804G>T	p.Asp602Tyr	missense	Exon 15 of 27	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.1852G>T	p.Asp618Tyr	missense	Exon 14 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.1852G>T	p.Asp618Tyr	missense	Exon 16 of 28	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.1804G>T	p.Asp602Tyr	missense	Exon 15 of 27	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.1852G>T	p.Asp618Tyr	missense	Exon 14 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246716 AF XY: 0.00000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457244 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724548

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 84680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110300

Other (OTH) AF: 0.00 AC: 0 AN: 60270

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.95	P
Vest4		0.28
MutPred		0.68		Loss of glycosylation at S599 (P = 0.0565)
MVP		0.44
MPC		0.029
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.11
gMVP		0.54
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: 24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs186218301; hg19: chr3-419601;