rs1300802922

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003072.5(SMARCA4):​c.2682G>A​(p.Thr894Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,370 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: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SMARCA4
NM_003072.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -4.28
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 19-11021790-G-A is Benign according to our data. Variant chr19-11021790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.28 with no splicing effect.
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA4NM_001387283.1 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 36 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 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.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 36 NM_001387283.1 ENSP00000495368.1 Q9HBD4
SMARCA4ENST00000344626.10 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 35 1 NM_003072.5 ENSP00000343896.4 P51532-1
SMARCA4ENST00000643549.1 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 35 ENSP00000493975.1 A0A2R8Y4P4
SMARCA4ENST00000541122.6 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 20 of 35 5 ENSP00000445036.2 P51532-4
SMARCA4ENST00000643296.1 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 34 ENSP00000496635.1 P51532-4
SMARCA4ENST00000644737.1 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 19 of 34 ENSP00000495548.1 P51532-4
SMARCA4ENST00000589677.5 linkc.2682G>A p.Thr894Thr synonymous_variant Exon 20 of 35 5 ENSP00000464778.1 P51532-3
SMARCA4ENST00000643995.1 linkc.2094G>A p.Thr698Thr synonymous_variant Exon 16 of 32 ENSP00000496004.1 A0A2R8YGG3
SMARCA4ENST00000644963.1 linkc.1326G>A p.Thr442Thr synonymous_variant Exon 12 of 28 ENSP00000495599.1 A0A2R8YG32
SMARCA4ENST00000644065.1 linkc.1407G>A p.Thr469Thr synonymous_variant Exon 12 of 27 ENSP00000493615.1 A0A2R8Y440
SMARCA4ENST00000642350.1 linkc.1167G>A p.Thr389Thr synonymous_variant Exon 11 of 27 ENSP00000495355.1 A0A2R8Y6N0
SMARCA4ENST00000643857.1 linkc.1035G>A p.Thr345Thr synonymous_variant Exon 10 of 25 ENSP00000494159.1 A0A2R8Y526

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250568
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461370
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727008
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:2
Jan 08, 2016
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. -

Aug 10, 2021
Sema4, Sema4
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

Rhabdoid tumor predisposition syndrome 2 Benign:1
Nov 27, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
3.7
DANN
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1300802922; hg19: chr19-11132466; COSMIC: COSV60808753; API