rs777886082
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000057.4(BLM):βc.1270_1272delβ(p.Leu424del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. S422S) has been classified as Likely benign.
Frequency
Consequence
NM_000057.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.1270_1272del | p.Leu424del | inframe_deletion | 7/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.1270_1272del | p.Leu424del | inframe_deletion | 7/22 | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250558Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135410
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460238Hom.: 0 AF XY: 0.00000826 AC XY: 6AN XY: 726150
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Bloom syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 21, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This variant, c.1270_1272del, results in the deletion of 1 amino acid(s) of the BLM protein (p.Leu424del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs777886082, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 454073). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 11, 2022 | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/250558 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.1270_1272delCTT variant (also known as p.L424del) is located in coding exon 6 of the BLM gene. This variant results from an in-frame CTT deletion at nucleotide positions 1270 to 1272. This results in the in-frame deletion of a leucine at codon 424. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at