Genetic Variant SBF1:c.*112C>T (chr22-50447030-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002972.4(SBF1):c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 938,200 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 31 hom. )

Consequence

SBF1
NM_002972.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.379

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-50447030-G-A is Benign according to our data. Variant chr22-50447030-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1193044.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00596 (908/152254) while in subpopulation NFE AF= 0.00871 (592/67986). AF 95% confidence interval is 0.00813. There are 3 homozygotes in gnomad4. There are 476 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SBF1	NM_002972.4 link	c.*112C>T	3_prime_UTR_variant	Exon 41 of 41	ENST00000380817.8	NP_002963.2	O95248-5
SBF1	NM_001410794.1 link	c.*112C>T	3_prime_UTR_variant	Exon 41 of 41		NP_001397723.1
SBF1	NM_001365819.1 link	c.*112C>T	3_prime_UTR_variant	Exon 40 of 40		NP_001352748.1
SBF1	NM_001410795.1 link	c.*112C>T	3_prime_UTR_variant	Exon 40 of 40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817 link	c.*112C>T		3_prime_UTR_variant	Exon 41 of 41	1	NM_002972.4	ENSP00000370196.2		O95248-5

Frequencies

GnomAD3 genomes

AF:

0.00596

AC:

907

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00871

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00681

AC:

5352

AN:

785946

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

2697

AN XY:

403148

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00285

Gnomad4 EAS exome

AF:

0.0000306

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00815

Gnomad4 OTH exome

AF:

0.00521

GnomAD4 genome

AF:

0.00596

AC:

908

AN:

152254

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

476

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0141

Gnomad4 NFE

AF:

0.00871

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00453

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 21, 2018

GeneDx

Significance: Likely 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

-0.68

CADD

Benign

8.6

DANN

Benign

0.96

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over