chr19-11024327-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001387283.1(SMARCA4):c.2974-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,605,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★★).
Frequency
Consequence
NM_001387283.1 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.2974-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000646693.2 | |||
SMARCA4 | NM_003072.5 | c.2974-4G>A | 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.2974-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003072.5 | P4 | |||
SMARCA4 | ENST00000646693.2 | c.2974-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001387283.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000136 AC: 34AN: 250612Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135728
GnomAD4 exome AF: 0.0000255 AC: 37AN: 1453068Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11AN XY: 723418
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74476
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 10, 2021 | - - |
Intellectual disability, autosomal dominant 16 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Rhabdoid tumor predisposition syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 13, 2023 | - - |
SMARCA4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 21, 2021 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at