chr19-11041974-C-T

Position:

• chr19-11041974-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003072.5(SMARCA4):​c.4424+414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 152,126 control chromosomes in the GnomAD database, including 595 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 0.069 (595 hom., cov: 32)
• Consequence: SMARCA4 NM_003072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4520+414C>T		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4424+414C>T		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4520+414C>T		intron_variant			NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4424+414C>T		intron_variant		1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4430+414C>T		intron_variant				ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4334+414C>T		intron_variant		5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4334+414C>T		intron_variant				ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4334+414C>T		intron_variant				ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4334+414C>T		intron_variant		5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.3845+414C>T		intron_variant				ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3077+414C>T		intron_variant				ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3059+414C>T		intron_variant				ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.2918+414C>T		intron_variant				ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2786+414C>T		intron_variant				ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.590+414C>T		intron_variant		3		ENSP00000495197.1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10504 AN: 152008 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0791

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

GnomAD4 genome AF: 0.0693 AC: 10542 AN: 152126 Hom.: 595 Cov.: 32 AF XY: 0.0721 AC XY: 5365 AN XY: 74364

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0446 Hom.: 71

Bravo AF: 0.0757

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2072382; hg19: chr19-11152650;