rs117084604
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003073.5(SMARCB1):c.1116G>A(p.Thr372=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003073.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.1116G>A | p.Thr372= | splice_region_variant, synonymous_variant | 8/9 | ENST00000644036.2 | NP_003064.2 | |
SMARCB1 | NM_001362877.2 | c.1170G>A | p.Thr390= | splice_region_variant, synonymous_variant | 8/9 | NP_001349806.1 | ||
SMARCB1 | NM_001317946.2 | c.1143G>A | p.Thr381= | splice_region_variant, synonymous_variant | 8/9 | NP_001304875.1 | ||
SMARCB1 | NM_001007468.3 | c.1089G>A | p.Thr363= | splice_region_variant, synonymous_variant | 8/9 | NP_001007469.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.1116G>A | p.Thr372= | splice_region_variant, synonymous_variant | 8/9 | NM_003073.5 | ENSP00000494049 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000342 AC: 86AN: 251260Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135846
GnomAD4 exome AF: 0.000274 AC: 400AN: 1461728Hom.: 1 Cov.: 32 AF XY: 0.000264 AC XY: 192AN XY: 727154
GnomAD4 genome AF: 0.000151 AC: 23AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74456
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SMARCB1: BP4, BP7, BS1 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 07, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2017 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at