rs41300676
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001033855.3(DCLRE1C):c.1893C>T(p.Pro631Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,614,068 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0044 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0057 ( 29 hom. )
Consequence
DCLRE1C
NM_001033855.3 synonymous
NM_001033855.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.839
Genes affected
DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. 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=-0.81).
BP6
Variant 10-14908594-G-A is Benign according to our data. Variant chr10-14908594-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-14908594-G-A is described in Lovd as [Likely_benign]. Variant chr10-14908594-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.839 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00439 (668/152202) while in subpopulation NFE AF= 0.00629 (428/68016). AF 95% confidence interval is 0.0058. There are 3 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DCLRE1C | NM_001033855.3 | c.1893C>T | p.Pro631Pro | synonymous_variant | 14/14 | ENST00000378278.7 | NP_001029027.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DCLRE1C | ENST00000378278.7 | c.1893C>T | p.Pro631Pro | synonymous_variant | 14/14 | 1 | NM_001033855.3 | ENSP00000367527.2 |
Frequencies
GnomAD3 genomes AF: 0.00437 AC: 665AN: 152084Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00375 AC: 942AN: 251202Hom.: 4 AF XY: 0.00355 AC XY: 482AN XY: 135722
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GnomAD4 exome AF: 0.00568 AC: 8299AN: 1461866Hom.: 29 Cov.: 32 AF XY: 0.00550 AC XY: 4002AN XY: 727234
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GnomAD4 genome AF: 0.00439 AC: 668AN: 152202Hom.: 3 Cov.: 31 AF XY: 0.00417 AC XY: 310AN XY: 74418
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 05, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | DCLRE1C: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 24, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 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, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Histiocytic medullary reticulosis Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Severe combined immunodeficiency due to DCLRE1C deficiency;C2700553:Histiocytic medullary reticulosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 17, 2022 | - - |
Computational scores
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Name
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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