Variant chr22-23786942-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.363

Variant links:

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]

SMARCB1 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE	Protein
SMARCB1	NM_003073.5 linkuse as main transcript	upstream_gene_variant	ENST00000644036.2	NP_003064.2
SMARCB1	NM_001007468.3 linkuse as main transcript	upstream_gene_variant		NP_001007469.1
SMARCB1	NM_001317946.2 linkuse as main transcript	upstream_gene_variant		NP_001304875.1
SMARCB1	NM_001362877.2 linkuse as main transcript	upstream_gene_variant		NP_001349806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2 linkuse as main transcript			upstream_gene_variant			NM_003073.5	ENSP00000494049	A1	Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16424

AN:

152188

Hom.:

919

Cov.:

show subpopulations

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.:

AF XY:

0.122

AC XY:

19734

AN XY:

161372

show subpopulations

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.:

AF XY:

0.109

AC XY:

8119

AN XY:

74480

show subpopulations

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.:

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

LINK: link

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

DANN

Benign

0.97

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over