NM_001387283.1:c.4521-5369C>T

Variant names:

• chr19-11052886-C-T
• rs1529729
• NM_001387283.1:c.4521-5369C>T

Variant summary

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

The NM_001387283.1(SMARCA4):​c.4521-5369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,020 control chromosomes in the GnomAD database, including 26,279 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 0.58 (26279 hom., cov: 31)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 35 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4521-5369C>T		intron_variant	Intron 31 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4425-5369C>T		intron_variant	Intron 30 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4521-5369C>T		intron_variant	Intron 31 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4425-5369C>T		intron_variant	Intron 30 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4431-5369C>T		intron_variant	Intron 30 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4335-5369C>T		intron_variant	Intron 30 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4335-5369C>T		intron_variant	Intron 29 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4335-5369C>T		intron_variant	Intron 29 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4335-5372C>T		intron_variant	Intron 30 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.3846-5369C>T		intron_variant	Intron 27 of 31			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3078-5372C>T		intron_variant	Intron 23 of 27			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3060-5372C>T		intron_variant	Intron 22 of 26			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.2919-5369C>T		intron_variant	Intron 22 of 26			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2787-5369C>T		intron_variant	Intron 21 of 24			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.591-5369C>T		intron_variant	Intron 4 of 7	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88406 AN: 151902 Hom.: 26250 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.582 AC: 88483 AN: 152020 Hom.: 26279 Cov.: 31 AF XY: 0.578 AC XY: 42967 AN XY: 74304

African (AFR) AF: 0.701 AC: 29062 AN: 41456

American (AMR) AF: 0.478 AC: 7290 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3846 AN: 5162

South Asian (SAS) AF: 0.494 AC: 2373 AN: 4806

European-Finnish (FIN) AF: 0.536 AC: 5682 AN: 10594

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36914 AN: 67968

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.551 Hom.: 104461

Bravo AF: 0.586

Asia WGS AF: 0.589 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.28
PhyloP100		-1.2
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: rs1529729; hg19: chr19-11163562;