19-11003031-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001387283.1(SMARCA4):c.1815T>C(p.Pro605=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 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, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.1815T>C | p.Pro605= | splice_region_variant, synonymous_variant | 12/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.1815T>C | p.Pro605= | splice_region_variant, synonymous_variant | 12/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.1815T>C | p.Pro605= | splice_region_variant, synonymous_variant | 12/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.1815T>C | p.Pro605= | splice_region_variant, synonymous_variant | 12/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251440Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135890
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461834Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727206
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 06, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2015 | 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. - |
SMARCA4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 30, 2022 | 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