Genetic Variant SBF1:c.*158_*162delCGCCC (chr22-50446979-CGGGCG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_002972.4(SBF1):c.*158_*162delCGCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 720,662 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00063 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 4 hom. )

Consequence

SBF1
NM_002972.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000725 (417/575010) while in subpopulation SAS AF = 0.00134 (81/60646). AF 95% confidence interval is 0.0011. There are 4 homozygotes in GnomAdExome4. There are 217 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

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.158_162delCGCCC	3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
SBF1	NM_001410794.1		c.158_162delCGCCC	3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
SBF1	NM_001365819.1		c.158_162delCGCCC	3_prime_UTR	Exon 40 of 40	NP_001352748.1	O95248-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SBF1	ENST00000380817.8	TSL:1 MANE Select	c.158_162delCGCCC	3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
SBF1	ENST00000418590.4	TSL:1	c.158_162delCGCCC	3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
SBF1	ENST00000931646.1		c.158_162delCGCCC	3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes

AF:

0.000632

AC:

AN:

145550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00734

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000741

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000694

Gnomad OTH

AF:

0.000985

GnomAD4 exome

AF:

0.000725

AC:

417

AN:

575010

Hom.:

AF XY:

0.000709

AC XY:

217

AN XY:

306002

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

15944

American (AMR)

AF:

0.000123

AC:

AN:

32538

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

132

AN:

19062

East Asian (EAS)

AF:

0.000188

AC:

AN:

31858

South Asian (SAS)

AF:

0.00134

AC:

AN:

60646

European-Finnish (FIN)

AF:

0.0000571

AC:

AN:

34996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2432

European-Non Finnish (NFE)

AF:

0.000461

AC:

160

AN:

346718

Other (OTH)

AF:

0.000714

AC:

AN:

30816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

114

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

AF:

0.000632

AC:

AN:

145652

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

71090

show subpopulations

African (AFR)

AF:

0.000324

AC:

AN:

40146

American (AMR)

AF:

0.000136

AC:

AN:

14716

Ashkenazi Jewish (ASJ)

AF:

0.00734

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

4408

South Asian (SAS)

AF:

0.000742

AC:

AN:

4044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9424

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000694

AC:

AN:

66290

Other (OTH)

AF:

0.000975

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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22-50446979-CGGGCGGGGCG-CGGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over