chr3-326074-G-C

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Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006614.4(CHL1):​c.197+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,555,454 control chromosomes in the GnomAD database, including 52,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14431 hom., cov: 32)
Exomes 𝑓: 0.21 ( 38541 hom. )

Consequence

CHL1
NM_006614.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0960
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 3-326074-G-C is Benign according to our data. Variant chr3-326074-G-C is described in ClinVar as [Benign]. Clinvar id is 1676925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHL1NM_006614.4 linkuse as main transcriptc.197+10G>C intron_variant ENST00000256509.7 NP_006605.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHL1ENST00000256509.7 linkuse as main transcriptc.197+10G>C intron_variant 1 NM_006614.4 ENSP00000256509 P3O00533-2

Frequencies

GnomAD3 genomes
AF:
0.347
AC:
52653
AN:
151724
Hom.:
14381
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.762
Gnomad AMI
AF:
0.164
Gnomad AMR
AF:
0.206
Gnomad ASJ
AF:
0.134
Gnomad EAS
AF:
0.00948
Gnomad SAS
AF:
0.192
Gnomad FIN
AF:
0.149
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.209
Gnomad OTH
AF:
0.309
GnomAD3 exomes
AF:
0.209
AC:
51471
AN:
246746
Hom.:
8634
AF XY:
0.202
AC XY:
26985
AN XY:
133508
show subpopulations
Gnomad AFR exome
AF:
0.775
Gnomad AMR exome
AF:
0.131
Gnomad ASJ exome
AF:
0.137
Gnomad EAS exome
AF:
0.00557
Gnomad SAS exome
AF:
0.193
Gnomad FIN exome
AF:
0.149
Gnomad NFE exome
AF:
0.206
Gnomad OTH exome
AF:
0.206
GnomAD4 exome
AF:
0.212
AC:
298008
AN:
1403612
Hom.:
38541
Cov.:
23
AF XY:
0.210
AC XY:
147292
AN XY:
701592
show subpopulations
Gnomad4 AFR exome
AF:
0.782
Gnomad4 AMR exome
AF:
0.141
Gnomad4 ASJ exome
AF:
0.137
Gnomad4 EAS exome
AF:
0.0118
Gnomad4 SAS exome
AF:
0.193
Gnomad4 FIN exome
AF:
0.152
Gnomad4 NFE exome
AF:
0.211
Gnomad4 OTH exome
AF:
0.225
GnomAD4 genome
AF:
0.347
AC:
52760
AN:
151842
Hom.:
14431
Cov.:
32
AF XY:
0.336
AC XY:
24971
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.762
Gnomad4 AMR
AF:
0.205
Gnomad4 ASJ
AF:
0.134
Gnomad4 EAS
AF:
0.00931
Gnomad4 SAS
AF:
0.192
Gnomad4 FIN
AF:
0.149
Gnomad4 NFE
AF:
0.209
Gnomad4 OTH
AF:
0.306
Alfa
AF:
0.246
Hom.:
1180
Bravo
AF:
0.367
Asia WGS
AF:
0.134
AC:
470
AN:
3476

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxApr 12, 2022- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
CHL1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This variant is classified as 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
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.5
DANN
Benign
0.40

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: rs162734; hg19: chr3-367757; API