Genetic Variant SMARCB1:c.500+234C>G (chr22-23801315-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003073.5(SMARCB1):c.500+234C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 719,486 control chromosomes in the GnomAD database, including 265,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 50617 hom., cov: 31)

Exomes 𝑓: 0.87 ( 215070 hom. )

Consequence

SMARCB1
NM_003073.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.772

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 22-23801315-C-G is Benign according to our data. Variant chr22-23801315-C-G is described in ClinVar as [Benign]. Clinvar id is 133392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5 link	c.500+234C>G	intron_variant	Intron 4 of 8	ENST00000644036.2	NP_003064.2	Q12824-1
SMARCB1	NM_001362877.2 link	c.554+180C>G	intron_variant	Intron 4 of 8		NP_001349806.1
SMARCB1	NM_001317946.2 link	c.527+180C>G	intron_variant	Intron 4 of 8		NP_001304875.1	G5E975Q9H836
SMARCB1	NM_001007468.3 link	c.473+234C>G	intron_variant	Intron 4 of 8		NP_001007469.1	Q12824-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2 link	c.500+234C>G		intron_variant	Intron 4 of 8		NM_003073.5	ENSP00000494049.2		Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122022

AN:

151976

Hom.:

50624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.579

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.815

GnomAD3 exomes

AF:

0.831

AC:

109259

AN:

131416

Hom.:

46141

AF XY:

0.830

AC XY:

59366

AN XY:

71486

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.870

Gnomad EAS exome

AF:

0.705

Gnomad SAS exome

AF:

0.741

Gnomad FIN exome

AF:

0.940

Gnomad NFE exome

AF:

0.920

Gnomad OTH exome

AF:

0.856

GnomAD4 exome

AF:

0.865

AC:

490817

AN:

567392

Hom.:

215070

Cov.:

AF XY:

0.861

AC XY:

263562

AN XY:

306174

show subpopulations

Gnomad4 AFR exome

AF:

0.576

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.870

Gnomad4 EAS exome

AF:

0.662

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.937

Gnomad4 NFE exome

AF:

0.919

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.802

AC:

122041

AN:

152094

Hom.:

50617

Cov.:

AF XY:

0.802

AC XY:

59662

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.578

Gnomad4 AMR

AF:

0.851

Gnomad4 ASJ

AF:

0.876

Gnomad4 EAS

AF:

0.699

Gnomad4 SAS

AF:

0.710

Gnomad4 FIN

AF:

0.938

Gnomad4 NFE

AF:

0.917

Gnomad4 OTH

AF:

0.806

Alfa

AF:

0.861

Hom.:

6445

Bravo

AF:

0.787

Asia WGS

AF:

0.691

AC:

2401

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.84

DANN

Benign

0.47

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

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