rs183468503

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_030962.4(SBF2):​c.4799C>T​(p.Thr1600Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SBF2
NM_030962.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.14
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0061095953).
BP6
Variant 11-9789242-G-A is Benign according to our data. Variant chr11-9789242-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SBF2NM_030962.4 linkuse as main transcriptc.4799C>T p.Thr1600Ile missense_variant 35/40 ENST00000256190.13 NP_112224.1 Q86WG5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SBF2ENST00000256190.13 linkuse as main transcriptc.4799C>T p.Thr1600Ile missense_variant 35/401 NM_030962.4 ENSP00000256190.8 Q86WG5-1

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00732
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000485
AC:
122
AN:
251474
Hom.:
0
AF XY:
0.000471
AC XY:
64
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00636
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000115
AC:
168
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.000110
AC XY:
80
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00393
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00734
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000236
Hom.:
0
Bravo
AF:
0.000280
ExAC
AF:
0.000387
AC:
47
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 22, 2018- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 17, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsMar 10, 2020- -
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.066
Eigen_PC
Benign
0.089
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.0061
T
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.24
Sift
Benign
0.16
T
Sift4G
Benign
0.19
T
Polyphen
0.0
B
Vest4
0.12
MVP
0.77
MPC
0.19
ClinPred
0.053
T
GERP RS
5.0
Varity_R
0.073
gMVP
0.36

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.

Other links and lift over

dbSNP: rs183468503; hg19: chr11-9810789; API