rs1555773218

Variant names:

• chr19-11010375-TC-T
• rs1555773218
• NM_001387283.1:c.2124-3delC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_003072.5(SMARCA4):​c.2124-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMARCA4 NM_003072.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-11010375-TC-T is Benign according to our data. Variant chr19-11010375-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 470284.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.2124-3delC		splice_region_variant, intron_variant	Intron 14 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.2124-3delC		splice_region_variant, intron_variant	Intron 14 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.2124-5delC		splice_region_variant, intron_variant	Intron 14 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.2124-5delC		splice_region_variant, intron_variant	Intron 14 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.2124-5delC		splice_region_variant, intron_variant	Intron 14 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.2124-5delC		splice_region_variant, intron_variant	Intron 15 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.2124-5delC		splice_region_variant, intron_variant	Intron 14 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.2124-5delC		splice_region_variant, intron_variant	Intron 14 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.2124-5delC		splice_region_variant, intron_variant	Intron 15 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.1536-5delC		splice_region_variant, intron_variant	Intron 11 of 31			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.768-5delC		splice_region_variant, intron_variant	Intron 7 of 27			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.849-5delC		splice_region_variant, intron_variant	Intron 7 of 26			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.609-5delC		splice_region_variant, intron_variant	Intron 6 of 26			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.477-5delC		splice_region_variant, intron_variant	Intron 5 of 24			ENSP00000494159.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Sep 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1555773218; hg19: chr19-11121051;