9-2116037-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003070.5(SMARCA2):c.3672G>A(p.Glu1224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,202 control chromosomes in the GnomAD database, including 22,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.23 ( 7917 hom., cov: 32)
Exomes 𝑓: 0.12 ( 14711 hom. )
Consequence
SMARCA2
NM_003070.5 synonymous
NM_003070.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.191
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 9-2116037-G-A is Benign according to our data. Variant chr9-2116037-G-A is described in ClinVar as [Benign]. Clinvar id is 126346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.191 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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SMARCA2 | NM_003070.5 | c.3672G>A | p.Glu1224= | synonymous_variant | 25/34 | ENST00000349721.8 | |
SMARCA2 | NM_001289396.1 | c.3672G>A | p.Glu1224= | synonymous_variant | 25/34 | ||
SMARCA2 | NM_139045.4 | c.3672G>A | p.Glu1224= | synonymous_variant | 25/33 | ||
SMARCA2 | NM_001289397.2 | c.3498G>A | p.Glu1166= | synonymous_variant | 25/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA2 | ENST00000349721.8 | c.3672G>A | p.Glu1224= | synonymous_variant | 25/34 | 5 | NM_003070.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.234 AC: 35534AN: 151964Hom.: 7872 Cov.: 32
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GnomAD3 exomes AF: 0.123 AC: 30639AN: 249844Hom.: 4060 AF XY: 0.115 AC XY: 15499AN XY: 135106
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GnomAD4 exome AF: 0.115 AC: 168002AN: 1460120Hom.: 14711 Cov.: 30 AF XY: 0.113 AC XY: 81859AN XY: 726386
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GnomAD4 genome AF: 0.234 AC: 35634AN: 152082Hom.: 7917 Cov.: 32 AF XY: 0.227 AC XY: 16874AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2018 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 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 13, 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at