22-23836864-G-A

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

2

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]
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]

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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
SMARCB1NM_003073.5 linkc.*2684G>A 3_prime_UTR_variant 9/9 ENST00000644036.2 NP_003064.2 Q12824-1
DERL3NM_001002862.3 linkc.*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
SMARCB1ENST00000644036.2 linkc.*2684G>A 3_prime_UTR_variant 9/9 NM_003073.5 ENSP00000494049.2 Q12824-1
DERL3ENST00000318109 linkc.*5C>T 3_prime_UTR_variant 7/71 NM_001002862.3 ENSP00000315303.8 Q96Q80-1

Frequencies

GnomAD3 genomes
AF:
0.00250
AC:
381
AN:
152168
Hom.:
0
Cov.:
33
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.:
2
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.:
16
Cov.:
35
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.:
0
Cov.:
33
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.:
0
Bravo
AF:
0.00272
Asia WGS
AF:
0.00318
AC:
11
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2024SMARCB1: 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.

Other links and lift over

dbSNP: rs200378544; hg19: chr22-24179051; API