rs35782584

chr22-23801197-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003073.5(SMARCB1):c.500+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,396,810 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (11 hom.)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -2.86

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-23801197-C-T is Benign according to our data. Variant chr22-23801197-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00649 (989/152340) while in subpopulation AFR AF= 0.0221 (920/41578). AF 95% confidence interval is 0.0209. There are 12 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 989 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCB1	NM_003073.5	c.500+116C>T		intron_variant		ENST00000644036.2
SMARCB1	NM_001007468.3	c.473+116C>T		intron_variant
SMARCB1	NM_001317946.2	c.527+62C>T		intron_variant
SMARCB1	NM_001362877.2	c.554+62C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2	c.500+116C>T		intron_variant			NM_003073.5	A1

Frequencies

GnomAD3 genomes AF: 0.00650 AC: 989 AN: 152222 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00180 AC: 352 AN: 196096 Hom.: 2 AF XY: 0.00130 AC XY: 137 AN XY: 105386

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000691

Gnomad SAS exome AF: 0.000113

Gnomad FIN exome AF: 0.0000564

Gnomad NFE exome AF: 0.000217

Gnomad OTH exome AF: 0.000773

GnomAD4 exome AF: 0.000835 AC: 1039 AN: 1244470 Hom.: 11 Cov.: 17 AF XY: 0.000715 AC XY: 448 AN XY: 626770

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.00146

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000268

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.0000584

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00649 AC: 989 AN: 152340 Hom.: 12 Cov.: 32 AF XY: 0.00619 AC XY: 461 AN XY: 74494

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00403 Hom.: 1

Bravo AF: 0.00762

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2018

This variant is associated with the following publications: (PMID: 24728327) -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.068
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs35782584; hg19: chr22-24143384; COSMIC: COSV104371126; COSMIC: COSV104371126;