19-11033860-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_003072.5(SMARCA4):​c.3868C>T​(p.Leu1290Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Consequence

SMARCA4
NM_003072.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.95
Variant links:
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 -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 19-11033860-C-T is Benign according to our data. Variant chr19-11033860-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1112437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.95 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMARCA4NM_001387283.1 linkuse as main transcriptc.3868C>T p.Leu1290Leu synonymous_variant 27/36 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkuse as main transcriptc.3868C>T p.Leu1290Leu synonymous_variant 27/35 ENST00000344626.10 NP_003063.2 P51532-1A7E2E1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMARCA4ENST00000646693.2 linkuse as main transcriptc.3868C>T p.Leu1290Leu synonymous_variant 27/36 NM_001387283.1 ENSP00000495368.1 Q9HBD4
SMARCA4ENST00000344626.10 linkuse as main transcriptc.3868C>T p.Leu1290Leu synonymous_variant 27/351 NM_003072.5 ENSP00000343896.4 P51532-1
SMARCA4ENST00000643995.1 linkuse as main transcriptc.3280C>T p.Leu1094Leu synonymous_variant 24/32 ENSP00000496004.1 A0A2R8YGG3
SMARCA4ENST00000644963.1 linkuse as main transcriptc.2512C>T p.Leu838Leu synonymous_variant 20/28 ENSP00000495599.1 A0A2R8YG32
SMARCA4ENST00000642350.1 linkuse as main transcriptc.2353C>T p.Leu785Leu synonymous_variant 19/27 ENSP00000495355.1 A0A2R8Y6N0
SMARCA4ENST00000643857.1 linkuse as main transcriptc.2221C>T p.Leu741Leu synonymous_variant 18/25 ENSP00000494159.1 A0A2R8Y526
SMARCA4ENST00000643549.1 linkuse as main transcriptc.3775-263C>T intron_variant ENSP00000493975.1 A0A2R8Y4P4
SMARCA4ENST00000541122.6 linkuse as main transcriptc.3775-263C>T intron_variant 5 ENSP00000445036.2 P51532-4
SMARCA4ENST00000643296.1 linkuse as main transcriptc.3775-263C>T intron_variant ENSP00000496635.1 P51532-4
SMARCA4ENST00000644737.1 linkuse as main transcriptc.3775-263C>T intron_variant ENSP00000495548.1 P51532-4
SMARCA4ENST00000589677.5 linkuse as main transcriptc.3775-263C>T intron_variant 5 ENSP00000464778.1 P51532-3
SMARCA4ENST00000644065.1 linkuse as main transcriptc.2500-263C>T intron_variant ENSP00000493615.1 A0A2R8Y440
SMARCA4ENST00000538456.4 linkuse as main transcriptc.31-263C>T intron_variant 3 ENSP00000495197.1 A0A2R8YFK5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 06, 2023- -
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2023This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
19
DANN
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11144536; API