chr22-23801105-C-G

Position:

chr22-23801105-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003073.5(SMARCB1):c.500+24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000914 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

SMARCB1
NM_003073.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:3O:1

Conservation

PhyloP100: -0.220

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 (MetaRNN=0.007938027).

BP6

Variant 22-23801105-C-G is Benign according to our data. Variant chr22-23801105-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 41778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23801105-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000827 (126/152310) while in subpopulation NFE AF= 0.00131 (89/68024). AF 95% confidence interval is 0.00109. There are 0 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMARCB1	NM_003073.5 linkuse as main transcript	c.500+24C>G		intron_variant		ENST00000644036.2
SMARCB1	NM_001362877.2 linkuse as main transcript	c.524C>G	p.Thr175Ser	missense_variant	4/9
SMARCB1	NM_001317946.2 linkuse as main transcript	c.497C>G	p.Thr166Ser	missense_variant	4/9
SMARCB1	NM_001007468.3 linkuse as main transcript	c.473+24C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2 linkuse as main transcript	c.500+24C>G		intron_variant			NM_003073.5	A1	Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

251400

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000923

AC:

1350

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

663

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152310

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000801

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00147

AC:

179

EpiCase

AF:

0.000927

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SMARCB1: PP2, PP3, BS1 -
Uncertain significance, no assertion criteria provided	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jul 13, 2012	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 03, 2023	- -

SMARCB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.0

DANN

Benign

0.61

DEOGEN2

Benign

0.0090

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.30

.;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.42

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.17

Sift

Benign

0.18

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.52

Gain of phosphorylation at S171 (P = 0.2011);.;

MVP

0.37

ClinPred

0.0037

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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