11-9832230-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 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 (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 id is 138965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9832230-G-C is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4 link	c.3646C>G	p.Gln1216Glu	missense_variant	Exon 27 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.3646C>G	p.Gln1216Glu	missense_variant	Exon 27 of 40	1	NM_030962.4	ENSP00000256190.8		Q86WG5-1

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

GnomAD3 exomes

AF:

0.0965

AC:

24246

AN:

251356

Hom.:

1345

AF XY:

0.0996

AC XY:

13533

AN XY:

135842

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 SAS exome

AF:

0.0999

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

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.0513

Gnomad4 ASJ exome

AF:

0.0798

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0816

AC:

12427

AN:

152252

Hom.:

597

Cov.:

AF XY:

0.0812

AC XY:

6048

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.0711

Gnomad4 ASJ

AF:

0.0735

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.0951

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0800

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

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 17, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Feb 03, 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

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

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

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

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