rs375787249
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001387283.1(SMARCA4):c.2275-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001387283.1 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.2275-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000646693.2 | |||
SMARCA4 | NM_003072.5 | c.2275-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.2275-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003072.5 | P4 | |||
SMARCA4 | ENST00000646693.2 | c.2275-10G>A | splice_polypyrimidine_tract_variant, intron_variant | NM_001387283.1 | |||||
ENST00000587831.1 | n.29-1685C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251392Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135878
GnomAD4 exome AF: 0.000230 AC: 336AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.000213 AC XY: 155AN XY: 727224
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 06, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
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 | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 22, 2020 | - - |
Coffin-Siris 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at