rs140145979
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005591.4(MRE11):c.845+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,611,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
MRE11
NM_005591.4 intron
NM_005591.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.22
Genes affected
MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [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=-0.74).
BP6
?
Variant 11-94471563-A-G is Benign according to our data. Variant chr11-94471563-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 182550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000302 (46/152236) while in subpopulation EAS AF= 0.0081 (42/5184). AF 95% confidence interval is 0.00616. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.845+11T>C | intron_variant | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.845+11T>C | intron_variant | 1 | NM_005591.4 | P3 | |||
MRE11 | ENST00000323977.7 | c.845+11T>C | intron_variant | 1 | |||||
MRE11 | ENST00000393241.8 | c.845+11T>C | intron_variant | 5 | A1 | ||||
MRE11 | ENST00000407439.7 | c.854+11T>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000316 AC: 48AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000727 AC: 182AN: 250218Hom.: 0 AF XY: 0.000724 AC XY: 98AN XY: 135374
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GnomAD4 exome AF: 0.000187 AC: 273AN: 1459466Hom.: 0 Cov.: 30 AF XY: 0.000194 AC XY: 141AN XY: 726058
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74450
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ataxia-telangiectasia-like disorder 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 13, 2016 | - - |
Ataxia-telangiectasia-like disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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