rs55791371

Variant names:

• chr19-11077477-A-C
• rs55791371
• ENST00000645236.1:c.1456-1520A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-11077477-A-C
• chr19-11077477-A-T

Variant summary

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

The ENST00000645236.1(SMARCA4):​c.1456-1520A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,116 control chromosomes in the GnomAD database, including 966 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 0.11 (966 hom., cov: 31)
• Consequence: SMARCA4 ENST00000645236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645236.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA4	ENST00000645236.1		c.1456-1520A>C		intron	N/A	ENSP00000494603.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16305 AN: 151998 Hom.: 967 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.107 AC: 16307 AN: 152116 Hom.: 966 Cov.: 31 AF XY: 0.107 AC XY: 7946 AN XY: 74350

African (AFR) AF: 0.111 AC: 4624 AN: 41472

American (AMR) AF: 0.0937 AC: 1428 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.00809 AC: 42 AN: 5190

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4834

European-Finnish (FIN) AF: 0.115 AC: 1214 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7819 AN: 68002

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.107 Hom.: 2136

Bravo AF: 0.109

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55791371; hg19: chr19-11188153;