rs200850440
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_000057.4(BLM):āc.2838A>Gā(p.Thr946=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,614,166 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T946T) has been classified as Likely benign.
Frequency
Consequence
NM_000057.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.2838A>G | p.Thr946= | synonymous_variant | 15/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.2838A>G | p.Thr946= | synonymous_variant | 15/22 | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152214Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251454Hom.: 1 AF XY: 0.0000883 AC XY: 12AN XY: 135896
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461834Hom.: 1 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727208
GnomAD4 genome ? AF: 0.000249 AC: 38AN: 152332Hom.: 1 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 19, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 24, 2016 | - - |
Bloom syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 24, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
BLM-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 14, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at