19-10961134-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001387283.1(SMARCA4):​c.-69C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 148,522 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SMARCA4
NM_001387283.1 5_prime_UTR

Scores

1
1

Clinical Significance

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

Conservation

PhyloP100: 0.137
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 -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21).
BP6
Variant 19-10961134-C-T is Benign according to our data. Variant chr19-10961134-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 328015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00197 (292/148522) while in subpopulation NFE AF= 0.00269 (179/66554). AF 95% confidence interval is 0.00237. There are 4 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMARCA4NM_001387283.1 linkuse as main transcriptc.-69C>T 5_prime_UTR_variant 1/36 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkuse as main transcriptc.-72C>T 5_prime_UTR_variant 1/35 ENST00000344626.10 NP_003063.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMARCA4ENST00000344626.10 linkuse as main transcriptc.-72C>T 5_prime_UTR_variant 1/351 NM_003072.5 ENSP00000343896 P4P51532-1
SMARCA4ENST00000646693.2 linkuse as main transcriptc.-69C>T 5_prime_UTR_variant 1/36 NM_001387283.1 ENSP00000495368

Frequencies

GnomAD3 genomes
AF:
0.00197
AC:
293
AN:
148414
Hom.:
4
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000611
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00134
Gnomad ASJ
AF:
0.00821
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00146
Gnomad FIN
AF:
0.00201
Gnomad MID
AF:
0.0258
Gnomad NFE
AF:
0.00269
Gnomad OTH
AF:
0.00344
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
26
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
12
Gnomad4 SAS exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
GnomAD4 genome
AF:
0.00197
AC:
292
AN:
148522
Hom.:
4
Cov.:
31
AF XY:
0.00189
AC XY:
137
AN XY:
72458
show subpopulations
Gnomad4 AFR
AF:
0.000610
Gnomad4 AMR
AF:
0.00133
Gnomad4 ASJ
AF:
0.00821
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00146
Gnomad4 FIN
AF:
0.00201
Gnomad4 NFE
AF:
0.00269
Gnomad4 OTH
AF:
0.00340
Alfa
AF:
0.00217
Hom.:
0
Bravo
AF:
0.00195

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Coffin-Siris syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
CADD
Benign
18
DANN
Uncertain
0.99
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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: rs559144002; hg19: chr19-11071810; API