rs759241720
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_003073.5(SMARCB1):c.582G>A(p.Glu194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,850 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 Likely benign (★★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SMARCB1
NM_003073.5 synonymous
NM_003073.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.91
Genes affected
SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 22-23803376-G-A is Benign according to our data. Variant chr22-23803376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 464330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23803376-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=2.91 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.582G>A | p.Glu194= | synonymous_variant | 5/9 | ENST00000644036.2 | |
SMARCB1 | NM_001362877.2 | c.636G>A | p.Glu212= | synonymous_variant | 5/9 | ||
SMARCB1 | NM_001317946.2 | c.609G>A | p.Glu203= | synonymous_variant | 5/9 | ||
SMARCB1 | NM_001007468.3 | c.555G>A | p.Glu185= | synonymous_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.582G>A | p.Glu194= | synonymous_variant | 5/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
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34
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251402Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461850Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727234
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GnomAD4 genome Cov.: 34
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2019 | 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. - |
Computational scores
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Name
Calibrated prediction
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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