19-11058300-G-C

Variant names:

• chr19-11058300-G-C
• rs750556885
• NM_001387283.1:c.4566G>C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003072.5(SMARCA4):​c.4470G>C​(p.Ser1490Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-11058300-G-C is Benign according to our data. Variant chr19-11058300-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3710601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4566G>C	p.Ser1522Ser	synonymous_variant	Exon 32 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4470G>C	p.Ser1490Ser	synonymous_variant	Exon 31 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4566G>C	p.Ser1522Ser	synonymous_variant	Exon 32 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4470G>C	p.Ser1490Ser	synonymous_variant	Exon 31 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4476G>C	p.Ser1492Ser	synonymous_variant	Exon 31 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4380G>C	p.Ser1460Ser	synonymous_variant	Exon 31 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4380G>C	p.Ser1460Ser	synonymous_variant	Exon 30 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4380G>C	p.Ser1460Ser	synonymous_variant	Exon 30 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4377G>C	p.Ser1459Ser	synonymous_variant	Exon 31 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.3891G>C	p.Ser1297Ser	synonymous_variant	Exon 28 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3120G>C	p.Ser1040Ser	synonymous_variant	Exon 24 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3102G>C	p.Ser1034Ser	synonymous_variant	Exon 23 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.2964G>C	p.Ser988Ser	synonymous_variant	Exon 23 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2832G>C	p.Ser944Ser	synonymous_variant	Exon 22 of 25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.636G>C	p.Ser212Ser	synonymous_variant	Exon 5 of 8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250956 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135824

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461284 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Jun 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.10
DANN	Benign	0.64

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: rs750556885; hg19: chr19-11168976;