NM_006614.4:c.1829A>C

Variant names:

• chr3-377895-A-C
• rs748576243
• NM_006614.4:c.1829A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006614.4(CHL1):​c.1829A>C​(p.His610Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12132877).
• BS2: High AC in GnomAdExome4 at 19 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.1829A>C	p.His610Pro	missense	Exon 16 of 28	NP_006605.2
	CHL1	NM_001253387.2		c.1781A>C	p.His594Pro	missense	Exon 15 of 27	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.1829A>C	p.His610Pro	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.1829A>C	p.His610Pro	missense	Exon 16 of 28	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.1781A>C	p.His594Pro	missense	Exon 15 of 27	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.1829A>C	p.His610Pro	missense	Exon 14 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250788 AF XY: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461190 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726898

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111544

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.020	D
Sift4G	Benign	0.061	T
Polyphen		0.067	B
Vest4		0.24
MutPred		0.41		Loss of catalytic residue at H594 (P = 0.0227)
MVP		0.21
MPC		0.015
ClinPred		0.092	T
GERP RS		3.3
Varity_R		0.30
gMVP		0.69
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748576243; hg19: chr3-419578;