rs587777977

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000491967.2(SMARCB1):n.968C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 667,950 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 39 hom., cov: 32)

Exomes 𝑓: 0.027 ( 249 hom. )

Consequence

SMARCB1
ENST00000491967.2 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.06

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
intellectual disability, autosomal dominant 15
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
rhabdoid tumor predisposition syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
SMARCB1-related schwannomatosis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
familial multiple meningioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial rhabdoid tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schwannomatosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SMARCB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 22-23801386-C-A is Benign according to our data. Variant chr22-23801386-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 133393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0209 (3181/152324) while in subpopulation NFE AF = 0.0294 (2002/68024). AF 95% confidence interval is 0.0284. There are 39 homozygotes in GnomAd4. There are 1613 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5 link	c.500+305C>A	intron_variant	Intron 4 of 8	ENST00000644036.2	NP_003064.2	Q12824-1
SMARCB1	NM_001362877.2 link	c.554+251C>A	intron_variant	Intron 4 of 8		NP_001349806.1
SMARCB1	NM_001317946.2 link	c.527+251C>A	intron_variant	Intron 4 of 8		NP_001304875.1	G5E975Q9H836
SMARCB1	NM_001007468.3 link	c.473+305C>A	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+305C>A		intron_variant	Intron 4 of 8		NM_003073.5	ENSP00000494049.2		Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3182

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0231

AC:

2963

AN:

128418

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.00473

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0374

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0268

AC:

13835

AN:

515626

Hom.:

249

Cov.:

AF XY:

0.0275

AC XY:

7691

AN XY:

279670

show subpopulations

African (AFR)

AF:

0.00540

AC:

AN:

15174

American (AMR)

AF:

0.0124

AC:

416

AN:

33504

Ashkenazi Jewish (ASJ)

AF:

0.0390

AC:

743

AN:

19054

East Asian (EAS)

AF:

0.00

AC:

AN:

29302

South Asian (SAS)

AF:

0.0285

AC:

1755

AN:

61564

European-Finnish (FIN)

AF:

0.0379

AC:

1112

AN:

29372

Middle Eastern (MID)

AF:

0.0354

AC:

138

AN:

3900

European-Non Finnish (NFE)

AF:

0.0300

AC:

8845

AN:

295164

Other (OTH)

AF:

0.0260

AC:

744

AN:

28592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

791

1583

2374

3166

3957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3181

AN:

152324

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1613

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00503

AC:

209

AN:

41578

American (AMR)

AF:

0.0156

AC:

238

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4828

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0294

AC:

2002

AN:

68024

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0267

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.0130

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 27, 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) -

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

AlphaMissense

Benign

0.10

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.28

(source)

DANN

Benign

0.56

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over