rs439132

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000234.3(LIG1):​c.-57-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,537,140 control chromosomes in the GnomAD database, including 4,454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.095 ( 1645 hom., cov: 31)
Exomes 𝑓: 0.027 ( 2809 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08
Variant links:
Genes affected
LIG1 (HGNC:6598): (DNA ligase 1) This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIG1NM_000234.3 linkuse as main transcriptc.-57-34A>G intron_variant ENST00000263274.12 NP_000225.1 P18858-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIG1ENST00000263274.12 linkuse as main transcriptc.-57-34A>G intron_variant 1 NM_000234.3 ENSP00000263274.6 P18858-1

Frequencies

GnomAD3 genomes
AF:
0.0948
AC:
14382
AN:
151656
Hom.:
1645
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.264
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0575
Gnomad ASJ
AF:
0.0115
Gnomad EAS
AF:
0.186
Gnomad SAS
AF:
0.100
Gnomad FIN
AF:
0.0539
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00653
Gnomad OTH
AF:
0.0740
GnomAD3 exomes
AF:
0.0560
AC:
14071
AN:
251156
Hom.:
1067
AF XY:
0.0525
AC XY:
7130
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.267
Gnomad AMR exome
AF:
0.0451
Gnomad ASJ exome
AF:
0.0117
Gnomad EAS exome
AF:
0.169
Gnomad SAS exome
AF:
0.0938
Gnomad FIN exome
AF:
0.0514
Gnomad NFE exome
AF:
0.00657
Gnomad OTH exome
AF:
0.0374
GnomAD4 exome
AF:
0.0266
AC:
36785
AN:
1385366
Hom.:
2809
Cov.:
23
AF XY:
0.0274
AC XY:
19008
AN XY:
693430
show subpopulations
Gnomad4 AFR exome
AF:
0.288
Gnomad4 AMR exome
AF:
0.0466
Gnomad4 ASJ exome
AF:
0.0111
Gnomad4 EAS exome
AF:
0.203
Gnomad4 SAS exome
AF:
0.0915
Gnomad4 FIN exome
AF:
0.0466
Gnomad4 NFE exome
AF:
0.00424
Gnomad4 OTH exome
AF:
0.0411
GnomAD4 genome
AF:
0.0950
AC:
14411
AN:
151774
Hom.:
1645
Cov.:
31
AF XY:
0.0966
AC XY:
7166
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.264
Gnomad4 AMR
AF:
0.0572
Gnomad4 ASJ
AF:
0.0115
Gnomad4 EAS
AF:
0.186
Gnomad4 SAS
AF:
0.0994
Gnomad4 FIN
AF:
0.0539
Gnomad4 NFE
AF:
0.00653
Gnomad4 OTH
AF:
0.0756
Alfa
AF:
0.0249
Hom.:
538
Bravo
AF:
0.102
Asia WGS
AF:
0.148
AC:
514
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.011
DANN
Benign
0.53

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs439132; hg19: chr19-48668914; COSMIC: COSV54390231; COSMIC: COSV54390231; API