rs3730849
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000234.3(LIG1):c.17+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,596,792 control chromosomes in the GnomAD database, including 111,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 8109 hom., cov: 31)
Exomes 𝑓: 0.37 ( 103020 hom. )
Consequence
LIG1
NM_000234.3 intron
NM_000234.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.22
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]
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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=-0.9).
BP6
?
Variant 19-48165538-G-A is Benign according to our data. Variant chr19-48165538-G-A is described in ClinVar as [Benign]. Clinvar id is 403038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIG1 | NM_000234.3 | c.17+12C>T | intron_variant | ENST00000263274.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIG1 | ENST00000263274.12 | c.17+12C>T | intron_variant | 1 | NM_000234.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.302 AC: 45850AN: 151714Hom.: 8106 Cov.: 31
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GnomAD3 exomes AF: 0.359 AC: 90308AN: 251440Hom.: 17560 AF XY: 0.363 AC XY: 49336AN XY: 135898
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GnomAD4 exome AF: 0.371 AC: 535969AN: 1444960Hom.: 103020 Cov.: 30 AF XY: 0.370 AC XY: 266516AN XY: 719868
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GnomAD4 genome ? AF: 0.302 AC: 45867AN: 151832Hom.: 8109 Cov.: 31 AF XY: 0.305 AC XY: 22647AN XY: 74164
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 57% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at