rs1555796040

Variant names:

• chr19-11059891-T-TC
• rs1555796040
• NM_001387283.1:c.4864+9dupC

Variant summary

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

The ENST00000344626.10(SMARCA4):​c.4768+6_4768+7insC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMARCA4 ENST00000344626.10 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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 19-11059891-T-TC is Benign according to our data. Variant chr19-11059891-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 537853.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.4864+9dupC		intron_variant	Intron 34 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4768+9dupC		intron_variant	Intron 33 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4864+6_4864+7insC		splice_region_variant, intron_variant	Intron 34 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4768+6_4768+7insC		splice_region_variant, intron_variant	Intron 33 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4774+6_4774+7insC		splice_region_variant, intron_variant	Intron 33 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4678+6_4678+7insC		splice_region_variant, intron_variant	Intron 33 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4678+6_4678+7insC		splice_region_variant, intron_variant	Intron 32 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4678+6_4678+7insC		splice_region_variant, intron_variant	Intron 32 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4675+6_4675+7insC		splice_region_variant, intron_variant	Intron 33 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.4189+6_4189+7insC		splice_region_variant, intron_variant	Intron 30 of 31			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3418+6_3418+7insC		splice_region_variant, intron_variant	Intron 26 of 27			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3400+6_3400+7insC		splice_region_variant, intron_variant	Intron 25 of 26			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.3262+6_3262+7insC		splice_region_variant, intron_variant	Intron 25 of 26			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.3028+6_3028+7insC		splice_region_variant, intron_variant	Intron 23 of 24			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.832+6_832+7insC		splice_region_variant, intron_variant	Intron 6 of 7	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461498 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

May 31, 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

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: rs1555796040; hg19: chr19-11170567;