rs6003904

chr22-23831207-A-G

Variant summary

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

The NM_003073.5(SMARCB1):c.987-2365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,048 control chromosomes in the GnomAD database, including 5,732 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 0.23 (5732 hom., cov: 32)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCB1	NM_003073.5	c.987-2365A>G		intron_variant		ENST00000644036.2
SMARCB1	NM_001007468.3	c.960-2365A>G		intron_variant
SMARCB1	NM_001317946.2	c.1014-2365A>G		intron_variant
SMARCB1	NM_001362877.2	c.1041-2365A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2	c.987-2365A>G		intron_variant			NM_003073.5	A1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34679 AN: 151930 Hom.: 5715 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.228 AC: 34727 AN: 152048 Hom.: 5732 Cov.: 32 AF XY: 0.226 AC XY: 16826 AN XY: 74358

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.214

Alfa AF: 0.198 Hom.: 782

Bravo AF: 0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.0070
Dann	Benign	0.60

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: rs6003904; hg19: chr22-24173394;