19-10986523-CGGCCCTGGCCCTGGCCCT-CGGCCCTGGCCCT
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS1
The NM_001387283.1(SMARCA4):c.708_713delTGGCCC(p.Gly237_Pro238del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000122 in 1,391,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P236P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SMARCA4
NM_001387283.1 disruptive_inframe_deletion
NM_001387283.1 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.83
Publications
1 publications found
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]
SMARCA4 Gene-Disease associations (from GenCC):
- Coffin-Siris syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
- intellectual disability, autosomal dominant 16Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- rhabdoid tumor predisposition syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- uterine corpus sarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- familial rhabdoid tumorInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary nonpolyposis colon cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_001387283.1
BP6
Variant 19-10986523-CGGCCCT-C is Benign according to our data. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573. Variant chr19-10986523-CGGCCCT-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 480573.
BS1
Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000122 (17/1391206) while in subpopulation SAS AF = 0.0000631 (5/79182). AF 95% confidence interval is 0.0000245. There are 0 homozygotes in GnomAdExome4. There are 8 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SMARCA4 | NM_001387283.1 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 36 | ENST00000646693.2 | NP_001374212.1 | |
| SMARCA4 | NM_003072.5 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SMARCA4 | ENST00000646693.2 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
| SMARCA4 | ENST00000344626.10 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
| SMARCA4 | ENST00000643549.1 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 35 | ENSP00000493975.1 | ||||
| SMARCA4 | ENST00000541122.6 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 5 of 35 | 5 | ENSP00000445036.2 | |||
| SMARCA4 | ENST00000643296.1 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 34 | ENSP00000496635.1 | ||||
| SMARCA4 | ENST00000644737.1 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 4 of 34 | ENSP00000495548.1 | ||||
| SMARCA4 | ENST00000589677.5 | c.708_713delTGGCCC | p.Gly237_Pro238del | disruptive_inframe_deletion | Exon 5 of 35 | 5 | ENSP00000464778.1 | |||
| SMARCA4 | ENST00000643995.1 | c.120_125delTGGCCC | p.Gly41_Pro42del | disruptive_inframe_deletion | Exon 1 of 32 | ENSP00000496004.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000144 AC: 2AN: 139340 AF XY: 0.0000264 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
139340
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000122 AC: 17AN: 1391206Hom.: 0 AF XY: 0.0000117 AC XY: 8AN XY: 686494 show subpopulations
GnomAD4 exome
AF:
AC:
17
AN:
1391206
Hom.:
AF XY:
AC XY:
8
AN XY:
686494
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31580
American (AMR)
AF:
AC:
0
AN:
35666
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
25116
East Asian (EAS)
AF:
AC:
0
AN:
35728
South Asian (SAS)
AF:
AC:
5
AN:
79182
European-Finnish (FIN)
AF:
AC:
0
AN:
41638
Middle Eastern (MID)
AF:
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
AC:
11
AN:
1078664
Other (OTH)
AF:
AC:
0
AN:
57938
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.437
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Dec 06, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant, c.708_713del, results in the deletion of 2 amino acid(s) of the SMARCA4 protein (p.Gly243_Pro244del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 480573). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
Feb 08, 2019
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek et al., 2016); but observed in multiple unaffected individuals undergoing testing at GeneDx; Has not been previously published as pathogenic or benign to our knowledge -
Hereditary cancer-predisposing syndrome Benign:1
Mar 16, 2021
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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