rs1555763625

Variant names:

• chr19-10996263-G-A
• rs1555763625
• NM_001387283.1:c.1644G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_003072.5(SMARCA4):​c.1644G>A​(p.Lys548Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 19-10996263-G-A is Benign according to our data. Variant chr19-10996263-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 11 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 10 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.1644G>A	p.Lys548Lys	synonymous_variant	Exon 11 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.1056G>A	p.Lys352Lys	synonymous_variant	Exon 7 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.288G>A	p.Lys96Lys	synonymous_variant	Exon 3 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.372G>A	p.Lys124Lys	synonymous_variant	Exon 3 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.132G>A	p.Lys44Lys	synonymous_variant	Exon 2 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.-4G>A		upstream_gene_variant				ENSP00000494159.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Jul 14, 2017

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	-0.31
CADD	Benign	14
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1555763625; hg19: chr19-11106939;