rs1122608

Positions:

• chr19-11052925-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001387283.1(SMARCA4):​c.4521-5330G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,202 control chromosomes in the GnomAD database, including 3,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3029 hom., cov: 32)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.330

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-11052925-G-T is Benign according to our data. Variant chr19-11052925-G-T is described in ClinVar as [Benign]. Clinvar id is 1602723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4521-5330G>T		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4425-5330G>T		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000344626.10	c.4425-5330G>T		intron_variant		1	NM_003072.5	ENSP00000343896	P4
SMARCA4	ENST00000646693.2	c.4521-5330G>T		intron_variant			NM_001387283.1	ENSP00000495368

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27071 AN: 152084 Hom.: 3034 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27057 AN: 152202 Hom.: 3029 Cov.: 32 AF XY: 0.177 AC XY: 13169 AN XY: 74380

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.181

Alfa AF: 0.230 Hom.: 3357

Bravo AF: 0.167

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.77

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: rs1122608; hg19: chr19-11163601;