3-319804-C-G

Variant names:

• chr3-319804-C-G
• rs139673243
• NM_006614.4:c.28C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006614.4(CHL1):​c.28C>G​(p.Leu10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,608,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.333
• Publications: 2 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054804683).
• BP6: Variant 3-319804-C-G is Benign according to our data. Variant chr3-319804-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 718047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 90 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.28C>G	p.Leu10Val	missense	Exon 3 of 28	NP_006605.2
	CHL1	NM_001253387.2		c.28C>G	p.Leu10Val	missense	Exon 3 of 27	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.28C>G	p.Leu10Val	missense	Exon 1 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.28C>G	p.Leu10Val	missense	Exon 3 of 28	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.28C>G	p.Leu10Val	missense	Exon 3 of 27	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.28C>G	p.Leu10Val	missense	Exon 1 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes AF: 0.000593 AC: 90 AN: 151874 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00533

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000814 AC: 203 AN: 249236 AF XY: 0.000579

Gnomad AFR exome AF: 0.000375

Gnomad AMR exome AF: 0.00568

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: 0.000495

GnomAD4 exome AF: 0.000212 AC: 308 AN: 1456130 Hom.: 1 Cov.: 28 AF XY: 0.000168 AC XY: 122 AN XY: 724568

African (AFR) AF: 0.000241 AC: 8 AN: 33152

American (AMR) AF: 0.00626 AC: 278 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1108234

Other (OTH) AF: 0.000250 AC: 15 AN: 60104

GnomAD4 genome AF: 0.000592 AC: 90 AN: 151990 Hom.: 0 Cov.: 32 AF XY: 0.000606 AC XY: 45 AN XY: 74288

African (AFR) AF: 0.000169 AC: 7 AN: 41512

American (AMR) AF: 0.00532 AC: 81 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67922

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.00120

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000544 AC: 66

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CHL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.026
DANN	Benign	0.65
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.33
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.056
Sift	Benign	0.087	T
Sift4G	Benign	0.11	T
Polyphen		0.20	B
Vest4		0.073
MVP		0.19
MPC		0.012
ClinPred		0.0071	T
GERP RS		-6.9
PromoterAI		-0.0088	Neutral
Varity_R		0.043
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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: rs139673243; hg19: chr3-361487;