22-23786986-G-A

Variant summary

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

The NM_003073.5(SMARCB1):c.-184G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 499,386 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

SMARCB1
NM_003073.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0100

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=-0.52).

BP6

Variant 22-23786986-G-A is Benign according to our data. Variant chr22-23786986-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 900500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00162 (247/152312) while in subpopulation AMR AF= 0.00222 (34/15306). AF 95% confidence interval is 0.00163. There are 6 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SMARCB1	NM_003073.5 linkuse as main transcript	c.-184G>A	5_prime_UTR_variant	1/9	ENST00000644036.2
SMARCB1	NM_001007468.3 linkuse as main transcript	c.-184G>A	5_prime_UTR_variant	1/9
SMARCB1	NM_001317946.2 linkuse as main transcript	c.-184G>A	5_prime_UTR_variant	1/9
SMARCB1	NM_001362877.2 linkuse as main transcript	c.-184G>A	5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2 linkuse as main transcript	c.-184G>A		5_prime_UTR_variant	1/9		NM_003073.5	A1	Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00162

AC:

563

AN:

347074

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

278

AN XY:

184764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000588

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.00183

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152312

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0178

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000847

Hom.:

Bravo

AF:

0.000657

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Schwannomatosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Rhabdoid tumor predisposition syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.97

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