rs774368488
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000057.4(BLM):c.3751+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000789 in 1,609,692 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 0 hom. )
Consequence
BLM
NM_000057.4 intron
NM_000057.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 15-90804368-A-C is Benign according to our data. Variant chr15-90804368-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 236817.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.3751+9A>C | intron_variant | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.3751+9A>C | intron_variant | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 250894Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135726
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GnomAD4 exome AF: 0.0000803 AC: 117AN: 1457458Hom.: 0 Cov.: 31 AF XY: 0.0000772 AC XY: 56AN XY: 725408
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74376
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Bloom syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 13, 2017 | - - |
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