19-10991328-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001387283.1(SMARCA4):c.1419+5G>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,584,464 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001387283.1 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.1419+5G>T | splice_donor_5th_base_variant, intron_variant | ENST00000646693.2 | |||
SMARCA4 | NM_003072.5 | c.1419+5G>T | splice_donor_5th_base_variant, intron_variant | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.1419+5G>T | splice_donor_5th_base_variant, intron_variant | 1 | NM_003072.5 | P4 | |||
SMARCA4 | ENST00000646693.2 | c.1419+5G>T | splice_donor_5th_base_variant, intron_variant | NM_001387283.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 709742
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74398
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2021 | The c.1419+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 7 in the SMARCA4 gene. This nucleotide position is well 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 | Apr 18, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at