rs1555753627

chr19-10986523-C-CGGCCCCGGCCCTchr19-10986523-C-CGGCCCG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001387283.1(SMARCA4):c.695_696insCGGCCCTGGCCC(p.Gly241_Pro244dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P230P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCA4 NM_001387283.1 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001387283.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA4	NM_001387283.1	c.695_696insCGGCCCTGGCCC	p.Gly241_Pro244dup	inframe_insertion	4/36	ENST00000646693.2
SMARCA4	NM_003072.5	c.695_696insCGGCCCTGGCCC	p.Gly241_Pro244dup	inframe_insertion	4/35	ENST00000344626.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA4	ENST00000344626.10	c.695_696insCGGCCCTGGCCC	p.Gly241_Pro244dup	inframe_insertion	4/35	1	NM_003072.5	P4
SMARCA4	ENST00000646693.2	c.695_696insCGGCCCTGGCCC	p.Gly241_Pro244dup	inframe_insertion	4/36		NM_001387283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11097199;