rs10964468
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003070.5(SMARCA2):c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,547,988 control chromosomes in the GnomAD database, including 8,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 1599 hom., cov: 33)
Exomes 𝑓: 0.094 ( 7123 hom. )
Consequence
SMARCA2
NM_003070.5 5_prime_UTR
NM_003070.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00500
Genes affected
SMARCA2 (HGNC:11098): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]
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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=-0.64).
BP6
?
Variant 9-2029018-G-A is Benign according to our data. Variant chr9-2029018-G-A is described in ClinVar as [Benign]. Clinvar id is 126341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA2 | NM_003070.5 | c.-5G>A | 5_prime_UTR_variant | 2/34 | ENST00000349721.8 | ||
SMARCA2 | NM_001289396.1 | c.-5G>A | 5_prime_UTR_variant | 2/34 | |||
SMARCA2 | NM_001289397.2 | c.-5G>A | 5_prime_UTR_variant | 2/33 | |||
SMARCA2 | NM_139045.4 | c.-5G>A | 5_prime_UTR_variant | 2/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA2 | ENST00000349721.8 | c.-5G>A | 5_prime_UTR_variant | 2/34 | 5 | NM_003070.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.130 AC: 19743AN: 152192Hom.: 1590 Cov.: 33
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GnomAD3 exomes AF: 0.115 AC: 17070AN: 149066Hom.: 1394 AF XY: 0.108 AC XY: 8586AN XY: 79660
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GnomAD4 exome AF: 0.0940 AC: 131232AN: 1395678Hom.: 7123 Cov.: 33 AF XY: 0.0922 AC XY: 63467AN XY: 688540
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GnomAD4 genome ? AF: 0.130 AC: 19787AN: 152310Hom.: 1599 Cov.: 33 AF XY: 0.129 AC XY: 9610AN XY: 74470
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2016 | This alteration is classified as 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. - |
Nicolaides-Baraitser syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2018 | - - |
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