chr19-11041336-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003072.5(SMARCA4):​c.4200C>T​(p.Ile1400Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,611,750 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SMARCA4
NM_003072.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.48
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 -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 19-11041336-C-T is Benign according to our data. Variant chr19-11041336-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 470392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.48 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000197 (3/152118) while in subpopulation EAS AF= 0.000386 (2/5186). AF 95% confidence interval is 0.0000683. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA4NM_001387283.1 linkc.4296C>T p.Ile1432Ile synonymous_variant Exon 31 of 36 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkc.4200C>T p.Ile1400Ile synonymous_variant Exon 30 of 35 ENST00000344626.10 NP_003063.2 P51532-1A7E2E1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA4ENST00000646693.2 linkc.4296C>T p.Ile1432Ile synonymous_variant Exon 31 of 36 NM_001387283.1 ENSP00000495368.1 Q9HBD4
SMARCA4ENST00000344626.10 linkc.4200C>T p.Ile1400Ile synonymous_variant Exon 30 of 35 1 NM_003072.5 ENSP00000343896.4 P51532-1
SMARCA4ENST00000643549.1 linkc.4206C>T p.Ile1402Ile synonymous_variant Exon 30 of 35 ENSP00000493975.1 A0A2R8Y4P4
SMARCA4ENST00000541122.6 linkc.4110C>T p.Ile1370Ile synonymous_variant Exon 30 of 35 5 ENSP00000445036.2 P51532-4
SMARCA4ENST00000643296.1 linkc.4110C>T p.Ile1370Ile synonymous_variant Exon 29 of 34 ENSP00000496635.1 P51532-4
SMARCA4ENST00000644737.1 linkc.4110C>T p.Ile1370Ile synonymous_variant Exon 29 of 34 ENSP00000495548.1 P51532-4
SMARCA4ENST00000589677.5 linkc.4110C>T p.Ile1370Ile synonymous_variant Exon 30 of 35 5 ENSP00000464778.1 P51532-3
SMARCA4ENST00000643995.1 linkc.3621C>T p.Ile1207Ile synonymous_variant Exon 27 of 32 ENSP00000496004.1 A0A2R8YGG3
SMARCA4ENST00000644963.1 linkc.2853C>T p.Ile951Ile synonymous_variant Exon 23 of 28 ENSP00000495599.1 A0A2R8YG32
SMARCA4ENST00000644065.1 linkc.2835C>T p.Ile945Ile synonymous_variant Exon 22 of 27 ENSP00000493615.1 A0A2R8Y440
SMARCA4ENST00000642350.1 linkc.2694C>T p.Ile898Ile synonymous_variant Exon 22 of 27 ENSP00000495355.1 A0A2R8Y6N0
SMARCA4ENST00000643857.1 linkc.2562C>T p.Ile854Ile synonymous_variant Exon 21 of 25 ENSP00000494159.1 A0A2R8Y526
SMARCA4ENST00000538456.4 linkc.366C>T p.Ile122Ile synonymous_variant Exon 4 of 8 3 ENSP00000495197.1 A0A2R8YFK5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000444
AC:
11
AN:
247844
Hom.:
0
AF XY:
0.0000447
AC XY:
6
AN XY:
134326
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000602
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1459632
Hom.:
0
Cov.:
32
AF XY:
0.0000207
AC XY:
15
AN XY:
726160
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000655
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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
Aug 21, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1
Aug 20, 2015
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Benign
12
DANN
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs577059244; hg19: chr19-11152012; COSMIC: COSV60793470; COSMIC: COSV60793470; API