15-90815245-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000057.4(BLM):c.4220G>C(p.Arg1407Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000057.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727232
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Bloom syndrome Uncertain:1
This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1407 of the BLM protein (p.Arg1407Thr). This variant is not present in population databases (gnomAD no frequency). 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: 1511147). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.R1407T variant (also known as c.4220G>C), located in coding exon 21 of the BLM gene, results from a G to C substitution at nucleotide position 4220. The arginine at codon 1407 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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