22-23786942-G-T

Position:

• chr22-23786942-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000407422.8(SMARCB1):​c.-228G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 460,204 control chromosomes in the GnomAD database, including 3,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (919 hom., cov: 34)
  • Exomes 𝑓: 0.12 (2455 hom.)
• Consequence: SMARCB1 ENST00000407422.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.363

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 22-23786942-G-T is Benign according to our data. Variant chr22-23786942-G-T is described in ClinVar as [Benign]. Clinvar id is 677083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCB1	NM_003073.5			upstream_gene_variant		ENST00000644036.2	NP_003064.2
SMARCB1	NM_001007468.3			upstream_gene_variant			NP_001007469.1
SMARCB1	NM_001317946.2			upstream_gene_variant			NP_001304875.1
SMARCB1	NM_001362877.2			upstream_gene_variant			NP_001349806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2			upstream_gene_variant			NM_003073.5	ENSP00000494049	A1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16424 AN: 152188 Hom.: 919 Cov.: 34

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.119 AC: 36696 AN: 307900 Hom.: 2455 Cov.: 0 AF XY: 0.122 AC XY: 19734 AN XY: 161372

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.0856

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0294

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.108 AC: 16421 AN: 152304 Hom.: 919 Cov.: 34 AF XY: 0.109 AC XY: 8119 AN XY: 74480

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0978

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0446 Hom.: 52

Bravo AF: 0.102

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11704810; hg19: chr22-24129129;