rs1555753680

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001387283.1(SMARCA4):c.708_719delTGGCCCCGGCCC(p.Gly237_Pro240del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000144 in 1,389,190 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P236P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMARCA4
NM_001387283.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Publications

0 publications found

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]

SMARCA4 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
intellectual disability, autosomal dominant 16
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
rhabdoid tumor predisposition syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
uterine corpus sarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
familial rhabdoid tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SMARCA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001387283.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 35	ENST00000344626.10	NP_003063.2	P51532-1A7E2E1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMARCA4	ENST00000646693.2 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 36		NM_001387283.1	ENSP00000495368.1	Q9HBD4
SMARCA4	ENST00000344626.10 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 35	1	NM_003072.5	ENSP00000343896.4	P51532-1
SMARCA4	ENST00000643549.1 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 35			ENSP00000493975.1	A0A2R8Y4P4
SMARCA4	ENST00000541122.6 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 5 of 35	5		ENSP00000445036.2	P51532-4
SMARCA4	ENST00000643296.1 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 34			ENSP00000496635.1	P51532-4
SMARCA4	ENST00000644737.1 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 4 of 34			ENSP00000495548.1	P51532-4
SMARCA4	ENST00000589677.5 link	c.708_719delTGGCCCCGGCCC	p.Gly237_Pro240del	disruptive_inframe_deletion	Exon 5 of 35	5		ENSP00000464778.1	P51532-3
SMARCA4	ENST00000643995.1 link	c.120_131delTGGCCCCGGCCC	p.Gly41_Pro44del	disruptive_inframe_deletion	Exon 1 of 32			ENSP00000496004.1	A0A2R8YGG3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000733

AC:

AN:

136388

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389190

Hom.:

AF XY:

0.00000146

AC XY:

AN XY:

685600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31560

American (AMR)

AF:

0.00

AC:

AN:

35634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25120

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.00

AC:

AN:

79126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078554

Other (OTH)

AF:

0.0000173

AC:

AN:

57908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2

Uncertain:1

Nov 11, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 645836). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This variant, c.708_719del, results in the deletion of 4 amino acid(s) of the SMARCA4 protein (p.Gly241_Pro244del), but otherwise preserves the integrity of the reading frame. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over