rs1555754225
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_001387283.1(SMARCA4):βc.803_811delβ(p.Val268_Pro270del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000617 in 1,459,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. G267G) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000062 ( 0 hom. )
Consequence
SMARCA4
NM_001387283.1 inframe_deletion
NM_001387283.1 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.28
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 Likely_benign. Variant got -2 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001387283.1.
BS2
?
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.803_811del | p.Val268_Pro270del | inframe_deletion | 5/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.803_811del | p.Val268_Pro270del | inframe_deletion | 5/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.803_811del | p.Val268_Pro270del | inframe_deletion | 5/35 | 1 | NM_003072.5 | P4 | |
SMARCA4 | ENST00000646693.2 | c.803_811del | p.Val268_Pro270del | inframe_deletion | 5/36 | NM_001387283.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459550Hom.: 0 AF XY: 0.00000826 AC XY: 6AN XY: 726220
GnomAD4 exome
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6
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726220
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 13, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This variant, c.803_811del, results in the deletion of 3 amino acid(s) of the SMARCA4 protein (p.Val268_Pro270del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 480595). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Intellectual disability, autosomal dominant 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2024 | The c.803_811delTGCCCCCCG variant (also known as p.V268_P270del) is located in coding exon 4 of the SMARCA4 gene. This variant results from an in-frame deletion of 9 nucleotides (TGCCCCCCG) at nucleotide positions 803 to 811. This results in the in-frame deletion of 3 amino acids (VPP) at codons 268 to 270. The deleted amino acid positions are well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at