11-9839661-G-C

Position:

chr11-9839661-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030962.4(SBF2):c.3292C>G(p.Leu1098Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,614,040 control chromosomes in the GnomAD database, including 476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 32 hom., cov: 32)

Exomes 𝑓: 0.023 ( 444 hom. )

Consequence

SBF2
NM_030962.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.404

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:

ENSG00000255476 (HGNC:):

ENSG00000255476 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=0.005821973).

BP6

Variant 11-9839661-G-C is Benign according to our data. Variant chr11-9839661-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 138964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9839661-G-C is described in Lovd as [Benign]. Variant chr11-9839661-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0177 (2696/152264) while in subpopulation NFE AF= 0.0262 (1780/68022). AF 95% confidence interval is 0.0252. There are 32 homozygotes in gnomad4. There are 1272 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF2	NM_030962.4 linkuse as main transcript	c.3292C>G	p.Leu1098Val	missense_variant	26/40	ENST00000256190.13	NP_112224.1	Q86WG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13 linkuse as main transcript	c.3292C>G	p.Leu1098Val	missense_variant	26/40	1	NM_030962.4	ENSP00000256190.8		Q86WG5-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2698

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0204

AC:

5136

AN:

251482

Hom.:

AF XY:

0.0214

AC XY:

2909

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0329

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0237

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0226

AC:

33052

AN:

1461776

Hom.:

444

Cov.:

AF XY:

0.0231

AC XY:

16787

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00346

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0233

Gnomad4 FIN exome

AF:

0.0203

Gnomad4 NFE exome

AF:

0.0242

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0177

AC:

2696

AN:

152264

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1272

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0401

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0226

Hom.:

Bravo

AF:

0.0171

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0298

AC:

256

ExAC

AF:

0.0209

AC:

2539

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2014	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 08, 2017	- -

Charcot-Marie-Tooth disease type 4B2

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
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. -
Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.61

REVEL

Benign

0.067

Sift

Benign

0.89

Sift4G

Benign

0.79

Polyphen

0.87

Vest4

0.49

MPC

0.19

ClinPred

0.013

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.33

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