Genetic Variant SBF1:p.Val1876Leu (chr22-50447198-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002972.4(SBF1):c.5626G>T(p.Val1876Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1876M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SBF1
NM_002972.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Publications

0 publications found

Variant links:

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

SBF1 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4B3
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia, Ambry Genetics

SBF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13443965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002972.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBF1	NM_002972.4	MANE Select	c.5626G>T	p.Val1876Leu	missense	Exon 41 of 41	NP_002963.2	O95248-5
SBF1	NM_001410794.1		c.5629G>T	p.Val1877Leu	missense	Exon 41 of 41	NP_001397723.1	O95248-4
SBF1	NM_001365819.1		c.5551G>T	p.Val1851Leu	missense	Exon 40 of 40	NP_001352748.1	O95248-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBF1	ENST00000380817.8	TSL:1 MANE Select	c.5626G>T	p.Val1876Leu	missense	Exon 41 of 41	ENSP00000370196.2	O95248-5
SBF1	ENST00000418590.4	TSL:1	c.1222G>T	p.Val408Leu	missense	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
SBF1	ENST00000931646.1		c.5686G>T	p.Val1896Leu	missense	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461410

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.013

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

PhyloP100

1.6

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.98

REVEL

Benign

0.050

Sift

Benign

0.038

Sift4G

Uncertain

0.019

Vest4

0.27

MVP

0.19

ClinPred

0.59

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.20

gMVP

0.18

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over