rs867536416
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_001387283.1(SMARCA4):c.5012G>A(p.Arg1671His) variant causes a missense change. The variant allele was found at a frequency of 0.0000676 in 1,613,608 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1671C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387283.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.5012G>A | p.Arg1671His | missense_variant | 36/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.4916G>A | p.Arg1639His | missense_variant | 35/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.5012G>A | p.Arg1671His | missense_variant | 36/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.4916G>A | p.Arg1639His | missense_variant | 35/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250772Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135648
GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461426Hom.: 0 Cov.: 30 AF XY: 0.0000729 AC XY: 53AN XY: 727056
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 16 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 24, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 35962714) - |
Rhabdoid tumor predisposition syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2020 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at