rs1555795854
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PVS1_ModeratePM2BP6_Moderate
The NM_001387283.1(SMARCA4):c.4732-3dupC variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SMARCA4
NM_001387283.1 splice_acceptor, intron
NM_001387283.1 splice_acceptor, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.670
Publications
0 publications found
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]
SMARCA4 Gene-Disease associations (from GenCC):
- Coffin-Siris syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
- intellectual disability, autosomal dominant 16Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- rhabdoid tumor predisposition syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- uterine corpus sarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- familial rhabdoid tumorInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary nonpolyposis colon cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.02638889 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.6, offset of 0 (no position change), new splice context is: ccctggtgtctctgccccAGatc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 19-11059747-G-GC is Benign according to our data. Variant chr19-11059747-G-GC is described in ClinVar as Likely_benign. ClinVar VariationId is 537892.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.4732-3dupC | splice_acceptor_variant, intron_variant | Intron 33 of 35 | ENST00000646693.2 | NP_001374212.1 | ||
SMARCA4 | NM_003072.5 | c.4636-3dupC | splice_acceptor_variant, intron_variant | Intron 32 of 34 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4732-6_4732-5insC | splice_region_variant, intron_variant | Intron 33 of 35 | NM_001387283.1 | ENSP00000495368.1 | ||||
SMARCA4 | ENST00000344626.10 | c.4636-6_4636-5insC | splice_region_variant, intron_variant | Intron 32 of 34 | 1 | NM_003072.5 | ENSP00000343896.4 | |||
SMARCA4 | ENST00000643549.1 | c.4642-6_4642-5insC | splice_region_variant, intron_variant | Intron 32 of 34 | ENSP00000493975.1 | |||||
SMARCA4 | ENST00000541122.6 | c.4546-6_4546-5insC | splice_region_variant, intron_variant | Intron 32 of 34 | 5 | ENSP00000445036.2 | ||||
SMARCA4 | ENST00000643296.1 | c.4546-6_4546-5insC | splice_region_variant, intron_variant | Intron 31 of 33 | ENSP00000496635.1 | |||||
SMARCA4 | ENST00000644737.1 | c.4546-6_4546-5insC | splice_region_variant, intron_variant | Intron 31 of 33 | ENSP00000495548.1 | |||||
SMARCA4 | ENST00000589677.5 | c.4543-6_4543-5insC | splice_region_variant, intron_variant | Intron 32 of 34 | 5 | ENSP00000464778.1 | ||||
SMARCA4 | ENST00000643995.1 | c.4057-6_4057-5insC | splice_region_variant, intron_variant | Intron 29 of 31 | ENSP00000496004.1 | |||||
SMARCA4 | ENST00000644963.1 | c.3286-6_3286-5insC | splice_region_variant, intron_variant | Intron 25 of 27 | ENSP00000495599.1 | |||||
SMARCA4 | ENST00000644065.1 | c.3268-6_3268-5insC | splice_region_variant, intron_variant | Intron 24 of 26 | ENSP00000493615.1 | |||||
SMARCA4 | ENST00000642350.1 | c.3130-6_3130-5insC | splice_region_variant, intron_variant | Intron 24 of 26 | ENSP00000495355.1 | |||||
SMARCA4 | ENST00000643857.1 | c.2896-6_2896-5insC | splice_region_variant, intron_variant | Intron 22 of 24 | ENSP00000494159.1 | |||||
SMARCA4 | ENST00000538456.4 | c.700-6_700-5insC | splice_region_variant, intron_variant | Intron 5 of 7 | 3 | ENSP00000495197.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Benign:1
Sep 10, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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