rs2186369

chr22-23828809-T-G

Variant summary

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

The NM_003073.5(SMARCB1):c.986+3394T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,130 control chromosomes in the GnomAD database, including 2,458 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 0.17 (2458 hom., cov: 32)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

Genes affected

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCB1	NM_003073.5	c.986+3394T>G		intron_variant		ENST00000644036.2
SMARCB1	NM_001007468.3	c.959+3394T>G		intron_variant
SMARCB1	NM_001317946.2	c.1013+3394T>G		intron_variant
SMARCB1	NM_001362877.2	c.1040+3394T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2	c.986+3394T>G		intron_variant			NM_003073.5	A1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26177 AN: 152012 Hom.: 2459 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.172 AC: 26195 AN: 152130 Hom.: 2458 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74362

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0171

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.153

Alfa AF: 0.166 Hom.: 272

Bravo AF: 0.176

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.68

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: rs2186369; hg19: chr22-24170996;