rs543683431

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003072.5(SMARCA4):​c.3951+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000646 in 1,610,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

SMARCA4
NM_003072.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00004900
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.457
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-11034207-G-A is Benign according to our data. Variant chr19-11034207-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11034207-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000046 (7/152258) while in subpopulation EAS AF= 0.00058 (3/5174). AF 95% confidence interval is 0.000157. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA4NM_001387283.1 linkc.3951+7G>A splice_region_variant, intron_variant Intron 28 of 35 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkc.3951+7G>A splice_region_variant, intron_variant Intron 28 of 34 ENST00000344626.10 NP_003063.2 P51532-1A7E2E1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA4ENST00000646693.2 linkc.3951+7G>A splice_region_variant, intron_variant Intron 28 of 35 NM_001387283.1 ENSP00000495368.1 Q9HBD4
SMARCA4ENST00000344626.10 linkc.3951+7G>A splice_region_variant, intron_variant Intron 28 of 34 1 NM_003072.5 ENSP00000343896.4 P51532-1
SMARCA4ENST00000643549.1 linkc.3852+7G>A splice_region_variant, intron_variant Intron 27 of 34 ENSP00000493975.1 A0A2R8Y4P4
SMARCA4ENST00000541122.6 linkc.3852+7G>A splice_region_variant, intron_variant Intron 28 of 34 5 ENSP00000445036.2 P51532-4
SMARCA4ENST00000643296.1 linkc.3852+7G>A splice_region_variant, intron_variant Intron 27 of 33 ENSP00000496635.1 P51532-4
SMARCA4ENST00000644737.1 linkc.3852+7G>A splice_region_variant, intron_variant Intron 27 of 33 ENSP00000495548.1 P51532-4
SMARCA4ENST00000589677.5 linkc.3852+7G>A splice_region_variant, intron_variant Intron 28 of 34 5 ENSP00000464778.1 P51532-3
SMARCA4ENST00000643995.1 linkc.3363+7G>A splice_region_variant, intron_variant Intron 25 of 31 ENSP00000496004.1 A0A2R8YGG3
SMARCA4ENST00000644963.1 linkc.2595+7G>A splice_region_variant, intron_variant Intron 21 of 27 ENSP00000495599.1 A0A2R8YG32
SMARCA4ENST00000644065.1 linkc.2577+7G>A splice_region_variant, intron_variant Intron 20 of 26 ENSP00000493615.1 A0A2R8Y440
SMARCA4ENST00000642350.1 linkc.2436+7G>A splice_region_variant, intron_variant Intron 20 of 26 ENSP00000495355.1 A0A2R8Y6N0
SMARCA4ENST00000643857.1 linkc.2304+7G>A splice_region_variant, intron_variant Intron 19 of 24 ENSP00000494159.1 A0A2R8Y526
SMARCA4ENST00000538456.4 linkc.108+7G>A splice_region_variant, intron_variant Intron 2 of 7 3 ENSP00000495197.1 A0A2R8YFK5

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152140
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250608
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000665
AC:
97
AN:
1458050
Hom.:
0
Cov.:
30
AF XY:
0.0000744
AC XY:
54
AN XY:
725618
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00202
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152258
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1
Dec 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
Nov 01, 2022
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1
Aug 29, 2020
Sema4, Sema4
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.11
DANN
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000049
dbscSNV1_RF
Benign
0.034
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: rs543683431; hg19: chr19-11144883; API