Genetic Variant SBF1:c.1749+368T>C (chr22-50463961-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002972.4(SBF1):c.1749+368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,106 control chromosomes in the GnomAD database, including 38,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 38165 hom., cov: 33)

Consequence

SBF1
NM_002972.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.388

Publications

5 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
SBF1	NM_002972.4	MANE Select	c.1749+368T>C	intron	N/A	NP_002963.2	O95248-5
SBF1	NM_001410794.1		c.1752+368T>C	intron	N/A	NP_001397723.1	O95248-4
SBF1	NM_001365819.1		c.1752+368T>C	intron	N/A	NP_001352748.1	O95248-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SBF1	ENST00000380817.8	TSL:1 MANE Select	c.1749+368T>C	intron	N/A	ENSP00000370196.2	O95248-5
SBF1	ENST00000931646.1		c.1749+368T>C	intron	N/A	ENSP00000601705.1
SBF1	ENST00000967446.1		c.1752+368T>C	intron	N/A	ENSP00000637505.1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106600

AN:

151988

Hom.:

38106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.692

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.702

AC:

106724

AN:

152106

Hom.:

38165

Cov.:

AF XY:

0.705

AC XY:

52398

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.795

AC:

32981

AN:

41482

American (AMR)

AF:

0.702

AC:

10737

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2160

AN:

3468

East Asian (EAS)

AF:

0.962

AC:

4992

AN:

5188

South Asian (SAS)

AF:

0.544

AC:

2618

AN:

4816

European-Finnish (FIN)

AF:

0.715

AC:

7564

AN:

10586

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.637

AC:

43295

AN:

67958

Other (OTH)

AF:

0.697

AC:

1474

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1586

3172

4758

6344

7930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.668

Hom.:

95758

Bravo

AF:

0.712

Asia WGS

AF:

0.791

AC:

2751

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.1

(source)

DANN

Benign

0.35

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(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

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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