chr22-23801197-C-T

Variant names:

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+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,396,810 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 11 hom. )

Consequence

SMARCB1
NM_003073.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.86

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=-0.92).

BP6

Variant 22-23801197-C-T is Benign according to our data. Variant chr22-23801197-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00649 (989/152340) while in subpopulation AFR AF= 0.0221 (920/41578). AF 95% confidence interval is 0.0209. There are 12 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 989 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5 link	c.500+116C>T	intron_variant	Intron 4 of 8	ENST00000644036.2	NP_003064.2	Q12824-1
SMARCB1	NM_001362877.2 link	c.554+62C>T	intron_variant	Intron 4 of 8		NP_001349806.1
SMARCB1	NM_001317946.2 link	c.527+62C>T	intron_variant	Intron 4 of 8		NP_001304875.1	G5E975Q9H836
SMARCB1	NM_001007468.3 link	c.473+116C>T	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+116C>T		intron_variant	Intron 4 of 8		NM_003073.5	ENSP00000494049.2		Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

989

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00180

AC:

352

AN:

196096

Hom.:

AF XY:

0.00130

AC XY:

137

AN XY:

105386

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000691

Gnomad SAS exome

AF:

0.000113

Gnomad FIN exome

AF:

0.0000564

Gnomad NFE exome

AF:

0.000217

Gnomad OTH exome

AF:

0.000773

GnomAD4 exome

AF:

0.000835

AC:

1039

AN:

1244470

Hom.:

Cov.:

AF XY:

0.000715

AC XY:

448

AN XY:

626770

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.0000584

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00649

AC:

989

AN:

152340

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00403

Hom.:

Bravo

AF:

0.00762

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.92

CADD

Benign

0.068

DANN

Benign

0.54

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