rs750695358
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001033855.3(DCLRE1C):c.678+5G>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,613,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001033855.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DCLRE1C | NM_001033855.3 | c.678+5G>T | splice_donor_5th_base_variant, intron_variant | ENST00000378278.7 | NP_001029027.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DCLRE1C | ENST00000378278.7 | c.678+5G>T | splice_donor_5th_base_variant, intron_variant | 1 | NM_001033855.3 | ENSP00000367527 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000330 AC: 5AN: 151590Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251030Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135720
GnomAD4 exome AF: 0.000117 AC: 171AN: 1461802Hom.: 0 Cov.: 43 AF XY: 0.000105 AC XY: 76AN XY: 727196
GnomAD4 genome AF: 0.0000330 AC: 5AN: 151590Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3AN XY: 74022
ClinVar
Submissions by phenotype
Histiocytic medullary reticulosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Severe combined immunodeficiency due to DCLRE1C deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 14, 2018 | This sequence change falls in intron 8 of the DCLRE1C gene. It does not directly change the encoded amino acid sequence of the DCLRE1C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs750695358, ExAC 0.01%). This variant has not been reported in the literature in individuals with DCLRE1C-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at