rs926233307
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001387283.1(SMARCA4):c.3775-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 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: 33)
Consequence
SMARCA4
NM_001387283.1 splice_region, splice_polypyrimidine_tract, intron
NM_001387283.1 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01648
2
Clinical Significance
Conservation
PhyloP100: 3.49
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 -3 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 19-11033763-A-G is Benign according to our data. Variant chr19-11033763-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 480694.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.3775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000646693.2 | |||
SMARCA4 | NM_003072.5 | c.3775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.3775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003072.5 | P4 | |||
SMARCA4 | ENST00000646693.2 | c.3775-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001387283.1 | |||||
ENST00000620113.1 | n.37A>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 2
GnomAD4 exome
Cov.:
2
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
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 | Nov 13, 2020 | The c.3775-4A>G intronic variant results from an A to G substitution 4 nucleotides upstream from coding exon 26 in the SMARCA4 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Rhabdoid tumor predisposition syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at