rs56853707

chr22-50447464-CCA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002972.4(SBF1):c.5452-13_5452-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,610,878 control chromosomes in the GnomAD database, including 139,826 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12051 hom., cov: 0)
  • Exomes 𝑓: 0.41 (127775 hom.)
• Consequence: SBF1 NM_002972.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-50447464-CCA-C is Benign according to our data. Variant chr22-50447464-CCA-C is described in ClinVar as [Benign]. Clinvar id is 258880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50447464-CCA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBF1	NM_002972.4	c.5452-13_5452-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000380817.8
SBF1	NM_001365819.1	c.5377-13_5377-12del		splice_polypyrimidine_tract_variant, intron_variant
SBF1	NM_001410794.1	c.5455-13_5455-12del		splice_polypyrimidine_tract_variant, intron_variant
SBF1	NM_001410795.1	c.5374-13_5374-12del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF1	ENST00000380817.8	c.5452-13_5452-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002972.4	P3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56387 AN: 151472 Hom.: 12050 Cov.: 0

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.403

GnomAD3 exomes AF: 0.437 AC: 108803 AN: 249114 Hom.: 26063 AF XY: 0.431 AC XY: 58284 AN XY: 135160

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.511

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.781

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.410 AC: 597967 AN: 1459288 Hom.: 127775 AF XY: 0.408 AC XY: 296392 AN XY: 725948

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.372 AC: 56402 AN: 151590 Hom.: 12051 Cov.: 0 AF XY: 0.380 AC XY: 28109 AN XY: 74012

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.400

Alfa AF: 0.415 Hom.: 2488

Bravo AF: 0.365

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

Other links and lift over

dbSNP: rs56853707; hg19: chr22-50885893;