22-50456591-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002972.4(SBF1):c.3987G>A(p.Ala1329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,543,372 control chromosomes in the GnomAD database, including 43,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4437 hom., cov: 30)

Exomes 𝑓: 0.22 ( 39330 hom. )

Consequence

SBF1
NM_002972.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.12

Publications

19 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

SBF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 22-50456591-C-T is Benign according to our data. Variant chr22-50456591-C-T is described in ClinVar as Benign. ClinVar VariationId is 258879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF1	NM_002972.4 link	c.3987G>A	p.Ala1329Ala	synonymous_variant	Exon 30 of 41	ENST00000380817.8	NP_002963.2	O95248-5
SBF1	NM_001410794.1 link	c.3990G>A	p.Ala1330Ala	synonymous_variant	Exon 30 of 41		NP_001397723.1
SBF1	NM_001365819.1 link	c.3912G>A	p.Ala1304Ala	synonymous_variant	Exon 29 of 40		NP_001352748.1
SBF1	NM_001410795.1 link	c.3909G>A	p.Ala1303Ala	synonymous_variant	Exon 29 of 40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8 link	c.3987G>A	p.Ala1329Ala	synonymous_variant	Exon 30 of 41	1	NM_002972.4	ENSP00000370196.2		O95248-5

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31911

AN:

151890

Hom.:

4441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.285

AC:

45396

AN:

159552

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.0967

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.219

AC:

304539

AN:

1391362

Hom.:

39330

Cov.:

AF XY:

0.219

AC XY:

150160

AN XY:

686146

show subpopulations

African (AFR)

AF:

0.0968

AC:

3057

AN:

31582

American (AMR)

AF:

0.387

AC:

13553

AN:

34998

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

2996

AN:

22292

East Asian (EAS)

AF:

0.701

AC:

26549

AN:

37878

South Asian (SAS)

AF:

0.243

AC:

18176

AN:

74882

European-Finnish (FIN)

AF:

0.279

AC:

13412

AN:

48122

Middle Eastern (MID)

AF:

0.172

AC:

937

AN:

5438

European-Non Finnish (NFE)

AF:

0.197

AC:

212961

AN:

1078882

Other (OTH)

AF:

0.225

AC:

12898

AN:

57288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

12805

25610

38414

51219

64024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7638

15276

22914

30552

38190

<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

AF:

0.210

AC:

31916

AN:

152010

Hom.:

4437

Cov.:

AF XY:

0.217

AC XY:

16158

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.104

AC:

4329

AN:

41478

American (AMR)

AF:

0.299

AC:

4558

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

450

AN:

3470

East Asian (EAS)

AF:

0.707

AC:

3647

AN:

5156

South Asian (SAS)

AF:

0.254

AC:

1222

AN:

4818

European-Finnish (FIN)

AF:

0.276

AC:

2921

AN:

10574

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14080

AN:

67936

Other (OTH)

AF:

0.222

AC:

468

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1227

2453

3680

4906

6133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.200

Hom.:

646

Bravo

AF:

0.212

Asia WGS

AF:

0.395

AC:

1367

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 4B3

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.6

(source)

DANN

Benign

0.62

PhyloP100

1.1

PromoterAI

0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over