chr11-9832230-G-C

Variant names:

Variant summary

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

The NM_030962.4(SBF2):c.3646C>G(p.Gln1216Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,612,902 control chromosomes in the GnomAD database, including 9,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 597 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8670 hom. )

Consequence

SBF2
NM_030962.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.664

Publications

28 publications found

Variant links:

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4B2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P, Orphanet

SBF2 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 (MetaRNN=0.0014258623).

BP6

Variant 11-9832230-G-C is Benign according to our data. Variant chr11-9832230-G-C is described in ClinVar as Benign. ClinVar VariationId is 138965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBF2	NM_030962.4	MANE Select	c.3646C>G	p.Gln1216Glu	missense	Exon 27 of 40	NP_112224.1	Q86WG5-1
SBF2	NM_001386339.1		c.3646C>G	p.Gln1216Glu	missense	Exon 27 of 41	NP_001373268.1	A0A8I5KQ02
SBF2	NM_001424318.1		c.3682C>G	p.Gln1228Glu	missense	Exon 28 of 41	NP_001411247.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBF2	ENST00000256190.13	TSL:1 MANE Select	c.3646C>G	p.Gln1216Glu	missense	Exon 27 of 40	ENSP00000256190.8	Q86WG5-1
SBF2	ENST00000689128.1		c.3646C>G	p.Gln1216Glu	missense	Exon 27 of 41	ENSP00000509587.1	A0A8I5KQ02
SBF2	ENST00000675281.2		c.3646C>G	p.Gln1216Glu	missense	Exon 27 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes

AF:

0.0817

AC:

12429

AN:

152134

Hom.:

598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.0712

Gnomad ASJ

AF:

0.0735

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0955

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0770

GnomAD2 exomes

AF:

0.0965

AC:

24246

AN:

251356

AF XY:

0.0996

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.0798

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.107

AC:

155765

AN:

1460650

Hom.:

8670

Cov.:

AF XY:

0.106

AC XY:

77237

AN XY:

726668

show subpopulations

African (AFR)

AF:

0.0262

AC:

876

AN:

33470

American (AMR)

AF:

0.0513

AC:

2296

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0798

AC:

2084

AN:

26128

East Asian (EAS)

AF:

0.155

AC:

6138

AN:

39692

South Asian (SAS)

AF:

0.101

AC:

8718

AN:

86218

European-Finnish (FIN)

AF:

0.114

AC:

6099

AN:

53406

Middle Eastern (MID)

AF:

0.0765

AC:

441

AN:

5762

European-Non Finnish (NFE)

AF:

0.111

AC:

122896

AN:

1110908

Other (OTH)

AF:

0.103

AC:

6217

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6669

13338

20006

26675

33344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4504

9008

13512

18016

22520

<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:

0.0816

AC:

12427

AN:

152252

Hom.:

597

Cov.:

AF XY:

0.0812

AC XY:

6048

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0307

AC:

1274

AN:

41558

American (AMR)

AF:

0.0711

AC:

1087

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0735

AC:

255

AN:

3468

East Asian (EAS)

AF:

0.149

AC:

774

AN:

5178

South Asian (SAS)

AF:

0.0951

AC:

459

AN:

4824

European-Finnish (FIN)

AF:

0.106

AC:

1127

AN:

10610

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7182

AN:

68008

Other (OTH)

AF:

0.0800

AC:

169

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

582

1163

1745

2326

2908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.105

Hom.:

691

Bravo

AF:

0.0778

TwinsUK

AF:

0.117

AC:

433

ALSPAC

AF:

0.122

AC:

469

ESP6500AA

AF:

0.0282

AC:

124

ESP6500EA

AF:

0.110

AC:

945

ExAC

AF:

0.0985

AC:

11956

Asia WGS

AF:

0.128

AC:

442

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.105

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 4 (1)

Charcot-Marie-Tooth disease type 4B2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.42

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

0.66

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.59

REVEL

Benign

0.27

Sift

Benign

0.36

Sift4G

Benign

0.36

Polyphen

0.011

Vest4

0.088

MPC

0.20

ClinPred

0.0013

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.38

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over