2-58204275-G-C

Variant summary

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

The NM_018062.4(FANCL):​c.375-49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,318,008 control chromosomes in the GnomAD database, including 9,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1944 hom., cov: 32)
Exomes 𝑓: 0.11 ( 7961 hom. )

Consequence

FANCL
NM_018062.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.204
Variant links:
Genes affected
FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 2-58204275-G-C is Benign according to our data. Variant chr2-58204275-G-C is described in ClinVar as [Benign]. Clinvar id is 257494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FANCLNM_018062.4 linkc.375-49C>G intron_variant Intron 5 of 13 ENST00000233741.9 NP_060532.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FANCLENST00000233741.9 linkc.375-49C>G intron_variant Intron 5 of 13 1 NM_018062.4 ENSP00000233741.5 Q9NW38-1

Frequencies

GnomAD3 genomes
AF:
0.145
AC:
21950
AN:
151898
Hom.:
1933
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.249
Gnomad AMI
AF:
0.0779
Gnomad AMR
AF:
0.0867
Gnomad ASJ
AF:
0.0645
Gnomad EAS
AF:
0.200
Gnomad SAS
AF:
0.169
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.0971
Gnomad OTH
AF:
0.116
GnomAD3 exomes
AF:
0.118
AC:
29533
AN:
249512
Hom.:
2146
AF XY:
0.116
AC XY:
15719
AN XY:
135160
show subpopulations
Gnomad AFR exome
AF:
0.261
Gnomad AMR exome
AF:
0.0769
Gnomad ASJ exome
AF:
0.0658
Gnomad EAS exome
AF:
0.192
Gnomad SAS exome
AF:
0.147
Gnomad FIN exome
AF:
0.126
Gnomad NFE exome
AF:
0.0955
Gnomad OTH exome
AF:
0.0990
GnomAD4 exome
AF:
0.110
AC:
128216
AN:
1165992
Hom.:
7961
Cov.:
16
AF XY:
0.110
AC XY:
65628
AN XY:
594460
show subpopulations
Gnomad4 AFR exome
AF:
0.262
Gnomad4 AMR exome
AF:
0.0812
Gnomad4 ASJ exome
AF:
0.0659
Gnomad4 EAS exome
AF:
0.219
Gnomad4 SAS exome
AF:
0.147
Gnomad4 FIN exome
AF:
0.127
Gnomad4 NFE exome
AF:
0.0984
Gnomad4 OTH exome
AF:
0.110
GnomAD4 genome
AF:
0.145
AC:
21998
AN:
152016
Hom.:
1944
Cov.:
32
AF XY:
0.146
AC XY:
10834
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.250
Gnomad4 AMR
AF:
0.0871
Gnomad4 ASJ
AF:
0.0645
Gnomad4 EAS
AF:
0.200
Gnomad4 SAS
AF:
0.168
Gnomad4 FIN
AF:
0.123
Gnomad4 NFE
AF:
0.0971
Gnomad4 OTH
AF:
0.119
Alfa
AF:
0.116
Hom.:
250
Bravo
AF:
0.145
Asia WGS
AF:
0.220
AC:
765
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 03, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Fanconi anemia complementation group L Benign:1
Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.30
DANN
Benign
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs1404459; hg19: chr2-58431410; COSMIC: COSV52072777; API