rs4987069
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000234.3(LIG1):c.1131C>T(p.Gly377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,608,854 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0092 ( 9 hom., cov: 32)
Exomes 𝑓: 0.015 ( 230 hom. )
Consequence
LIG1
NM_000234.3 synonymous
NM_000234.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.40
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 19-48137645-G-A is Benign according to our data. Variant chr19-48137645-G-A is described in ClinVar as [Benign]. Clinvar id is 403036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.4 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0147 (21419/1456518) while in subpopulation NFE AF= 0.017 (18932/1111566). AF 95% confidence interval is 0.0168. There are 230 homozygotes in gnomad4_exome. There are 10313 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIG1 | NM_000234.3 | c.1131C>T | p.Gly377= | synonymous_variant | 13/28 | ENST00000263274.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIG1 | ENST00000263274.12 | c.1131C>T | p.Gly377= | synonymous_variant | 13/28 | 1 | NM_000234.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00918 AC: 1397AN: 152218Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00912 AC: 2220AN: 243422Hom.: 18 AF XY: 0.00891 AC XY: 1182AN XY: 132714
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GnomAD4 exome AF: 0.0147 AC: 21419AN: 1456518Hom.: 230 Cov.: 32 AF XY: 0.0142 AC XY: 10313AN XY: 724798
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GnomAD4 genome ? AF: 0.00917 AC: 1397AN: 152336Hom.: 9 Cov.: 32 AF XY: 0.00854 AC XY: 636AN XY: 74478
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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 submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | LIG1: BP4, BP7, BS1, BS2 - |
not specified Benign:1
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 - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at