rs7102464

Variant summary

Our verdict is Benign. Variant got -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. 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:5

Conservation

PhyloP100: 5.00

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:

(HGNC:):

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=0.001321584).

BP6

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

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/exons	MANE	UniProt
SBF2	NM_030962.4 linkuse as main transcript	c.2035G>A	p.Glu679Lys	missense_variant	18/40	ENST00000256190.13
LOC101928008	NR_120539.1 linkuse as main transcript	n.135+19015C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13 linkuse as main transcript	c.2035G>A	p.Glu679Lys	missense_variant	18/40	1	NM_030962.4	P3	Q86WG5-1
	ENST00000533659.1 linkuse as main transcript	n.134+19015C>T		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.0767

AC:

19291

AN:

251452

Hom.:

1178

AF XY:

0.0759

AC XY:

10316

AN XY:

135898

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 SAS exome

AF:

0.0135

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

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0408

Gnomad4 ASJ exome

AF:

0.0392

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.0888

GnomAD4 genome

AF:

0.0799

AC:

12158

AN:

152224

Hom.:

779

Cov.:

AF XY:

0.0818

AC XY:

6085

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.0628

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0970

Hom.:

2019

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 17, 2017

- -

Charcot-Marie-Tooth disease type 4B2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

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

MutationTaster

Benign

0.79

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

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

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