rs1805384
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_206937.2(LIG4):c.-28-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,142,904 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.035 ( 221 hom., cov: 32)
Exomes 𝑓: 0.0096 ( 198 hom. )
Consequence
LIG4
NM_206937.2 intron
NM_206937.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.104
Genes affected
LIG4 (HGNC:6601): (DNA ligase 4) The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
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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=-0.83).
BP6
Variant 13-108211333-A-G is Benign according to our data. Variant chr13-108211333-A-G is described in ClinVar as [Benign]. Clinvar id is 1247962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIG4 | NM_206937.2 | c.-28-37T>C | intron_variant | ENST00000442234.6 | NP_996820.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIG4 | ENST00000442234.6 | c.-28-37T>C | intron_variant | 1 | NM_206937.2 | ENSP00000402030.1 |
Frequencies
GnomAD3 genomes AF: 0.0349 AC: 5306AN: 152150Hom.: 221 Cov.: 32
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GnomAD4 exome AF: 0.00961 AC: 9519AN: 990636Hom.: 198 Cov.: 13 AF XY: 0.00955 AC XY: 4868AN XY: 509788
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GnomAD4 genome AF: 0.0349 AC: 5310AN: 152268Hom.: 221 Cov.: 32 AF XY: 0.0339 AC XY: 2523AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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