rs11085754

Variant names:

• chr19-11017920-A-G
• rs11085754
• NM_001387283.1:c.2439-1037A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387283.1(SMARCA4):​c.2439-1037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,828 control chromosomes in the GnomAD database, including 12,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (12929 hom., cov: 33)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 13 publications found

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]

SMARCA4 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
• intellectual disability, autosomal dominant 16

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• rhabdoid tumor predisposition syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• uterine corpus sarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• familial rhabdoid tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.2439-1037A>G		intron_variant	Intron 16 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.2439-1037A>G		intron_variant	Intron 16 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.2439-1037A>G		intron_variant	Intron 16 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.2439-1037A>G		intron_variant	Intron 16 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.2439-1037A>G		intron_variant	Intron 16 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.2439-1037A>G		intron_variant	Intron 17 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.2439-1037A>G		intron_variant	Intron 16 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.2439-1037A>G		intron_variant	Intron 16 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.2439-1037A>G		intron_variant	Intron 17 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.1851-1037A>G		intron_variant	Intron 13 of 31			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.1083-1037A>G		intron_variant	Intron 9 of 27			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.1164-1037A>G		intron_variant	Intron 9 of 26			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.924-1037A>G		intron_variant	Intron 8 of 26			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.792-1037A>G		intron_variant	Intron 7 of 24			ENSP00000494159.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 61990 AN: 151710 Hom.: 12883 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.409 AC: 62097 AN: 151828 Hom.: 12929 Cov.: 33 AF XY: 0.414 AC XY: 30714 AN XY: 74220

African (AFR) AF: 0.429 AC: 17682 AN: 41210

American (AMR) AF: 0.339 AC: 5191 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1341 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2935 AN: 5160

South Asian (SAS) AF: 0.545 AC: 2632 AN: 4826

European-Finnish (FIN) AF: 0.429 AC: 4544 AN: 10586

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26491 AN: 67974

Other (OTH) AF: 0.412 AC: 869 AN: 2108

Alfa AF: 0.399 Hom.: 7585

Bravo AF: 0.402

Asia WGS AF: 0.526 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.87
DANN	Benign	0.14
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11085754; hg19: chr19-11128596;