22-23801315-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000491967.2(SMARCB1):n.897C>G 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 0.852 in 719,486 control chromosomes in the GnomAD database, including 265,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 50617 hom., cov: 31)

Exomes 𝑓: 0.87 ( 215070 hom. )

Consequence

SMARCB1
ENST00000491967.2 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.772

Publications

7 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=-0.86).

BP6

Variant 22-23801315-C-G is Benign according to our data. Variant chr22-23801315-C-G is described in ClinVar as Benign. ClinVar VariationId is 133392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491967.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMARCB1	NM_003073.5	MANE Select	c.500+234C>G	intron	N/A	NP_003064.2
SMARCB1	NM_001362877.2		c.554+180C>G	intron	N/A	NP_001349806.1
SMARCB1	NM_001317946.2		c.527+180C>G	intron	N/A	NP_001304875.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMARCB1	ENST00000491967.2	TSL:1	n.897C>G	non_coding_transcript_exon	Exon 4 of 4
SMARCB1	ENST00000644036.2	MANE Select	c.500+234C>G	intron	N/A	ENSP00000494049.2
SMARCB1	ENST00000407422.8	TSL:1	c.473+234C>G	intron	N/A	ENSP00000383984.3

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122022

AN:

151976

Hom.:

50624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.579

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.815

GnomAD2 exomes

AF:

0.831

AC:

109259

AN:

131416

AF XY:

0.830

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.870

Gnomad EAS exome

AF:

0.705

Gnomad FIN exome

AF:

0.940

Gnomad NFE exome

AF:

0.920

Gnomad OTH exome

AF:

0.856

GnomAD4 exome

AF:

0.865

AC:

490817

AN:

567392

Hom.:

215070

Cov.:

AF XY:

0.861

AC XY:

263562

AN XY:

306174

show subpopulations

African (AFR)

AF:

0.576

AC:

9238

AN:

16048

American (AMR)

AF:

0.828

AC:

28695

AN:

34666

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

17481

AN:

20086

East Asian (EAS)

AF:

0.662

AC:

21238

AN:

32066

South Asian (SAS)

AF:

0.744

AC:

46315

AN:

62282

European-Finnish (FIN)

AF:

0.937

AC:

31034

AN:

33118

Middle Eastern (MID)

AF:

0.856

AC:

3511

AN:

4104

European-Non Finnish (NFE)

AF:

0.919

AC:

306703

AN:

333912

Other (OTH)

AF:

0.855

AC:

26602

AN:

31110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4199

8398

12597

16796

20995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1438

2876

4314

5752

7190

<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:

0.802

AC:

122041

AN:

152094

Hom.:

50617

Cov.:

AF XY:

0.802

AC XY:

59662

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.578

AC:

23950

AN:

41422

American (AMR)

AF:

0.851

AC:

12991

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.876

AC:

3039

AN:

3470

East Asian (EAS)

AF:

0.699

AC:

3614

AN:

5170

South Asian (SAS)

AF:

0.710

AC:

3425

AN:

4822

European-Finnish (FIN)

AF:

0.938

AC:

9954

AN:

10608

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.917

AC:

62368

AN:

68014

Other (OTH)

AF:

0.806

AC:

1701

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1050

2100

3151

4201

5251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.861

Hom.:

6445

Bravo

AF:

0.787

Asia WGS

AF:

0.691

AC:

2401

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.84

(source)

DANN

Benign

0.47

PhyloP100

-0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over