rs7102464

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.2035G>A(p.Glu679Lys) variant causes a missense change. The variant allele was found at a frequency of 0.102 in 1,613,964 control chromosomes in the GnomAD database, including 10,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 779 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9332 hom. )

Consequence

SBF2
NM_030962.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.00

Publications

29 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

SBF2 links:

ENSG00000255476 (HGNC:):

ENSG00000255476 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=0.001321584).

BP6

Variant 11-9858291-C-T is Benign according to our data. Variant chr11-9858291-C-T is described in ClinVar as Benign. ClinVar VariationId is 306602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4 link	c.2035G>A	p.Glu679Lys	missense_variant	Exon 18 of 40	ENST00000256190.13	NP_112224.1	Q86WG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13 link	c.2035G>A	p.Glu679Lys	missense_variant	Exon 18 of 40	1	NM_030962.4	ENSP00000256190.8		Q86WG5-1

Frequencies

GnomAD3 genomes

AF:

0.0799

AC:

12158

AN:

152108

Hom.:

779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0597

GnomAD2 exomes

AF:

0.0767

AC:

19291

AN:

251452

AF XY:

0.0759

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.0382

Gnomad ASJ exome

AF:

0.0359

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0735

GnomAD4 exome

AF:

0.104

AC:

151753

AN:

1461740

Hom.:

9332

Cov.:

AF XY:

0.101

AC XY:

73497

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.0143

AC:

480

AN:

33480

American (AMR)

AF:

0.0408

AC:

1825

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

1024

AN:

26132

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.0140

AC:

1208

AN:

86258

European-Finnish (FIN)

AF:

0.190

AC:

10169

AN:

53418

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.118

AC:

131623

AN:

1111870

Other (OTH)

AF:

0.0888

AC:

5365

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7192

14383

21575

28766

35958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4586

9172

13758

18344

22930

<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:

0.0799

AC:

12158

AN:

152224

Hom.:

779

Cov.:

AF XY:

0.0818

AC XY:

6085

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0197

AC:

817

AN:

41544

American (AMR)

AF:

0.0628

AC:

961

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0108

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.207

AC:

2194

AN:

10580

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7851

AN:

68004

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

539

1078

1617

2156

2695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0927

Hom.:

2596

Bravo

AF:

0.0660

TwinsUK

AF:

0.121

AC:

447

ALSPAC

AF:

0.120

AC:

464

ESP6500AA

AF:

0.0232

AC:

102

ESP6500EA

AF:

0.107

AC:

918

ExAC

AF:

0.0751

AC:

9122

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.101

EpiControl

AF:

0.0982

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 17, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 4B2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Charcot-Marie-Tooth disease type 4

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.057

Eigen

Benign

0.095

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

5.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.18

REVEL

Benign

0.12

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.058

MPC

0.20

ClinPred

0.019

GERP RS

4.3

Varity_R

0.11

gMVP

0.17

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over