rs75904516
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001387283.1(SMARCA4):c.2617-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,510,384 control chromosomes in the GnomAD database, including 1,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.051 ( 628 hom., cov: 33)
Exomes 𝑓: 0.012 ( 1022 hom. )
Consequence
SMARCA4
NM_001387283.1 intron
NM_001387283.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
Genes affected
SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 19-11021639-G-A is Benign according to our data. Variant chr19-11021639-G-A is described in ClinVar as [Benign]. Clinvar id is 133384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.2617-86G>A | intron_variant | ENST00000646693.2 | |||
SMARCA4 | NM_003072.5 | c.2617-86G>A | intron_variant | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.2617-86G>A | intron_variant | 1 | NM_003072.5 | P4 | |||
SMARCA4 | ENST00000646693.2 | c.2617-86G>A | intron_variant | NM_001387283.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0508 AC: 7736AN: 152196Hom.: 620 Cov.: 33
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GnomAD3 exomes AF: 0.0290 AC: 4290AN: 148064Hom.: 259 AF XY: 0.0320 AC XY: 2545AN XY: 79468
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GnomAD4 exome AF: 0.0118 AC: 16069AN: 1358070Hom.: 1022 Cov.: 24 AF XY: 0.0140 AC XY: 9410AN XY: 672334
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GnomAD4 genome ? AF: 0.0510 AC: 7770AN: 152314Hom.: 628 Cov.: 33 AF XY: 0.0513 AC XY: 3824AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2018 | This variant is associated with the following publications: (PMID: 24728327) - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2015 | This alteration is classified as 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at