rs774132615
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_003072.5(SMARCA4):c.1118+7delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,459,952 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
SMARCA4
NM_003072.5 splice_region, intron
NM_003072.5 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.46
Genes affected
SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is 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. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 19-10987928-AG-A is Benign according to our data. Variant chr19-10987928-AG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 415129.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000295 (43/1459952) while in subpopulation NFE AF= 0.0000378 (42/1111868). AF 95% confidence interval is 0.0000283. There are 0 homozygotes in gnomad4_exome. There are 17 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 43 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.1118+5delG | splice_region_variant, intron_variant | NM_001387283.1 | ENSP00000495368.1 | |||||
SMARCA4 | ENST00000344626.10 | c.1118+5delG | splice_region_variant, intron_variant | 1 | NM_003072.5 | ENSP00000343896.4 | ||||
SMARCA4 | ENST00000643549.1 | c.1118+5delG | splice_region_variant, intron_variant | ENSP00000493975.1 | ||||||
SMARCA4 | ENST00000541122.6 | c.1118+5delG | splice_region_variant, intron_variant | 5 | ENSP00000445036.2 | |||||
SMARCA4 | ENST00000643296.1 | c.1118+5delG | splice_region_variant, intron_variant | ENSP00000496635.1 | ||||||
SMARCA4 | ENST00000644737.1 | c.1118+5delG | splice_region_variant, intron_variant | ENSP00000495548.1 | ||||||
SMARCA4 | ENST00000589677.5 | c.1118+5delG | splice_region_variant, intron_variant | 5 | ENSP00000464778.1 | |||||
SMARCA4 | ENST00000643995.1 | c.530+5delG | splice_region_variant, intron_variant | ENSP00000496004.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239508Hom.: 0 AF XY: 0.00000764 AC XY: 1AN XY: 130858
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GnomAD4 exome AF: 0.0000295 AC: 43AN: 1459952Hom.: 0 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 726266
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2016 | - - |
Intellectual disability, autosomal dominant 16 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Rhabdoid tumor predisposition syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
SMARCA4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 05, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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