rs41296835
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_021141.4(XRCC5):c.*301A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 393,412 control chromosomes in the GnomAD database, including 33 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 0.010 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 6 hom. )
Consequence
XRCC5
NM_021141.4 3_prime_UTR
NM_021141.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.359
Genes affected
XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1571/152306) while in subpopulation AFR AF= 0.0362 (1503/41552). AF 95% confidence interval is 0.0347. There are 27 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1572 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC5 | NM_021141.4 | c.*301A>G | 3_prime_UTR_variant | 21/21 | ENST00000392132.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC5 | ENST00000392132.7 | c.*301A>G | 3_prime_UTR_variant | 21/21 | 1 | NM_021141.4 | P1 | ||
XRCC5 | ENST00000392133.7 | c.*301A>G | 3_prime_UTR_variant | 23/23 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0103 AC: 1572AN: 152188Hom.: 27 Cov.: 32
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GnomAD4 exome AF: 0.00118 AC: 284AN: 241106Hom.: 6 Cov.: 0 AF XY: 0.00111 AC XY: 141AN XY: 127342
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GnomAD4 genome ? AF: 0.0103 AC: 1571AN: 152306Hom.: 27 Cov.: 32 AF XY: 0.0100 AC XY: 746AN XY: 74486
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ClinVar
Not reported inComputational scores
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Name
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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