19-11039520-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001387283.1(SMARCA4):c.4233G>A(p.Gln1411Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SMARCA4
NM_001387283.1 synonymous
NM_001387283.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.730
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 -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (REVEL=0.058).
BP6
Variant 19-11039520-G-A is Benign according to our data. Variant chr19-11039520-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2732674.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.73 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4233G>A | p.Gln1411Gln | synonymous_variant | Exon 30 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000643549.1 | c.4134G>A | p.Gln1378Gln | synonymous_variant | Exon 29 of 35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000344626.10 | c.4171-1787G>A | intron_variant | Intron 29 of 34 | 1 | NM_003072.5 | ENSP00000343896.4 | |||
SMARCA4 | ENST00000541122.6 | c.4072-1778G>A | intron_variant | Intron 29 of 34 | 5 | ENSP00000445036.2 | ||||
SMARCA4 | ENST00000643296.1 | c.4072-1778G>A | intron_variant | Intron 28 of 33 | ENSP00000496635.1 | |||||
SMARCA4 | ENST00000644737.1 | c.4072-1778G>A | intron_variant | Intron 28 of 33 | ENSP00000495548.1 | |||||
SMARCA4 | ENST00000589677.5 | c.4072-1778G>A | intron_variant | Intron 29 of 34 | 5 | ENSP00000464778.1 | ||||
SMARCA4 | ENST00000643995.1 | c.3583-1778G>A | intron_variant | Intron 26 of 31 | ENSP00000496004.1 | |||||
SMARCA4 | ENST00000644963.1 | c.2815-1778G>A | intron_variant | Intron 22 of 27 | ENSP00000495599.1 | |||||
SMARCA4 | ENST00000644065.1 | c.2797-1778G>A | intron_variant | Intron 21 of 26 | ENSP00000493615.1 | |||||
SMARCA4 | ENST00000642350.1 | c.2656-1778G>A | intron_variant | Intron 21 of 26 | ENSP00000495355.1 | |||||
SMARCA4 | ENST00000643857.1 | c.2524-1778G>A | intron_variant | Intron 20 of 24 | ENSP00000494159.1 | |||||
SMARCA4 | ENST00000538456.4 | c.328-1778G>A | intron_variant | Intron 3 of 7 | 3 | ENSP00000495197.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152200
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1451306Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 721788
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1451306
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
721788
African (AFR)
AF:
AC:
0
AN:
32758
American (AMR)
AF:
AC:
0
AN:
42352
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25962
East Asian (EAS)
AF:
AC:
0
AN:
39098
South Asian (SAS)
AF:
AC:
0
AN:
83928
European-Finnish (FIN)
AF:
AC:
0
AN:
53296
Middle Eastern (MID)
AF:
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1108186
Other (OTH)
AF:
AC:
0
AN:
59980
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74352
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41446
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Benign:1
Jan 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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