rs738799

chr22-23816078-C-G

Variant summary

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

The NM_003073.5(SMARCB1):c.629-692C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 153,246 control chromosomes in the GnomAD database, including 21,825 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 0.51 (21593 hom., cov: 31)
  • Exomes 𝑓: 0.57 (232 hom.)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCB1	NM_003073.5	c.629-692C>G		intron_variant		ENST00000644036.2
SMARCB1	NM_001007468.3	c.602-692C>G		intron_variant
SMARCB1	NM_001317946.2	c.656-692C>G		intron_variant
SMARCB1	NM_001362877.2	c.683-692C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2	c.629-692C>G		intron_variant			NM_003073.5	A1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76902 AN: 151846 Hom.: 21597 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.572 AC: 733 AN: 1282 Hom.: 232 Cov.: 0 AF XY: 0.594 AC XY: 392 AN XY: 660

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.472

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.506 AC: 76895 AN: 151964 Hom.: 21593 Cov.: 31 AF XY: 0.508 AC XY: 37719 AN XY: 74270

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.536

Alfa AF: 0.562 Hom.: 3154

Bravo AF: 0.492

Asia WGS AF: 0.490 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.7
Dann	Benign	0.72

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: rs738799; hg19: chr22-24158265;