NM_001387283.1:c.696_713delTGGCCCTGGCCCTGGCCC

Variant names:

• chr19-10986523-CGGCCCTGGCCCTGGCCCT-C
• rs372601826
• NM_001387283.1:c.696_713delTGGCCCTGGCCCTGGCCC

Variant summary

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

The NM_001387283.1(SMARCA4):​c.696_713delTGGCCCTGGCCCTGGCCC​(p.Gly233_Pro238del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000719 in 1,391,208 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P232P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SMARCA4 NM_001387283.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 0 publications found

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

ACMG classification

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	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 5 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 4 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.696_713delTGGCCCTGGCCCTGGCCC	p.Gly233_Pro238del	disruptive_inframe_deletion	Exon 5 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.108_125delTGGCCCTGGCCCTGGCCC	p.Gly37_Pro42del	disruptive_inframe_deletion	Exon 1 of 32			ENSP00000496004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391208 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 686496

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078664

Other (OTH) AF: 0.00 AC: 0 AN: 57938

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

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

Other links and lift over

dbSNP: rs372601826; hg19: chr19-11097199;