chr3-319804-C-G

Position:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_006614.4(CHL1):ā€‹c.28C>Gā€‹(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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00059 ( 0 hom., cov: 32)
Exomes š‘“: 0.00021 ( 1 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

17

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.333
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
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 id is 718047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHL1NM_006614.4 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 3/28 ENST00000256509.7 NP_006605.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHL1ENST00000256509.7 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 3/281 NM_006614.4 ENSP00000256509 P3O00533-2

Frequencies

GnomAD3 genomes
AF:
0.000593
AC:
90
AN:
151874
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.000814
AC:
203
AN:
249236
Hom.:
1
AF XY:
0.000579
AC XY:
78
AN XY:
134762
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.000241
Gnomad4 AMR exome
AF:
0.00626
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000632
Gnomad4 OTH exome
AF:
0.000250
GnomAD4 genome
AF:
0.000592
AC:
90
AN:
151990
Hom.:
0
Cov.:
32
AF XY:
0.000606
AC XY:
45
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00532
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
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

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
CHL1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJun 18, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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;.;.;.;T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.56
T;T;T;T;T;T;T
MetaRNN
Benign
0.0055
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.56
N;N;N;N;N;N;.
REVEL
Benign
0.056
Sift
Benign
0.087
T;T;T;T;T;T;.
Sift4G
Benign
0.11
T;T;T;T;T;T;T
Polyphen
0.20
B;B;.;.;.;.;.
Vest4
0.073
MVP
0.19
MPC
0.012
ClinPred
0.0071
T
GERP RS
-6.9
Varity_R
0.043
gMVP
0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139673243; hg19: chr3-361487; API