rs35782584
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003073.5(SMARCB1):c.500+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,396,810 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0065 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 11 hom. )
Consequence
SMARCB1
NM_003073.5 intron
NM_003073.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.86
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 22-23801197-C-T is Benign according to our data. Variant chr22-23801197-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00649 (989/152340) while in subpopulation AFR AF= 0.0221 (920/41578). AF 95% confidence interval is 0.0209. There are 12 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 989 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.500+116C>T | intron_variant | ENST00000644036.2 | NP_003064.2 | |||
SMARCB1 | NM_001007468.3 | c.473+116C>T | intron_variant | NP_001007469.1 | ||||
SMARCB1 | NM_001317946.2 | c.527+62C>T | intron_variant | NP_001304875.1 | ||||
SMARCB1 | NM_001362877.2 | c.554+62C>T | intron_variant | NP_001349806.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.500+116C>T | intron_variant | NM_003073.5 | ENSP00000494049 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00650 AC: 989AN: 152222Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00180 AC: 352AN: 196096Hom.: 2 AF XY: 0.00130 AC XY: 137AN XY: 105386
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GnomAD4 exome AF: 0.000835 AC: 1039AN: 1244470Hom.: 11 Cov.: 17 AF XY: 0.000715 AC XY: 448AN XY: 626770
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GnomAD4 genome AF: 0.00649 AC: 989AN: 152340Hom.: 12 Cov.: 32 AF XY: 0.00619 AC XY: 461AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 24, 2018 | This variant is associated with the following publications: (PMID: 24728327) - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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