Variant 22-23836864-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003073.5(SMARCB1):c.*2684G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,459,896 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

SMARCB1
NM_003073.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.171

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:

DERL3 (HGNC:14236): (derlin 3) The protein encoded by this gene belongs to the derlin family, and resides in the endoplasmic reticulum (ER). Proteins that are unfolded or misfolded in the ER must be refolded or degraded to maintain the homeostasis of the ER. This protein appears to be involved in the degradation of misfolded glycoproteins in the ER. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

DERL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 22-23836864-G-A is Benign according to our data. Variant chr22-23836864-G-A is described in ClinVar as [Benign]. Clinvar id is 1711548.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 382 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCB1	NM_003073.5 link	c.*2684G>A		3_prime_UTR_variant	9/9	ENST00000644036.2	NP_003064.2	Q12824-1
DERL3	NM_001002862.3 link	c.*5C>T		3_prime_UTR_variant	7/7	ENST00000318109.12	NP_001002862.1	Q96Q80-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2 link	c.*2684G>A		3_prime_UTR_variant	9/9		NM_003073.5	ENSP00000494049.2		Q12824-1
DERL3	ENST00000318109 link	c.*5C>T		3_prime_UTR_variant	7/7	1	NM_001002862.3	ENSP00000315303.8		Q96Q80-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00271

AC:

216

AN:

79632

Hom.:

AF XY:

0.00270

AC XY:

106

AN XY:

39260

show subpopulations

Gnomad AFR exome

AF:

0.000420

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.00493

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00533

GnomAD4 exome

AF:

0.00360

AC:

4709

AN:

1307610

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2339

AN XY:

635422

show subpopulations

Gnomad4 AFR exome

AF:

0.000563

Gnomad4 AMR exome

AF:

0.00373

Gnomad4 ASJ exome

AF:

0.00622

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00176

Gnomad4 NFE exome

AF:

0.00398

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152286

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00371

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

SMARCB1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.48

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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