rs56853707

Variant names:

• chr22-50447464-CCA-C
• rs56853707
• NM_002972.4:c.5452-13_5452-12delTG

Your query was ambiguous. Multiple possible variants found:

• chr22-50447464-CCA-C
• chr22-50447464-CCA-CCACA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002972.4(SBF1):​c.5452-13_5452-12delTG variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.
• 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 rank	MANE	Protein	UniProt
SBF1	NM_002972.4	c.5452-13_5452-12delTG		intron_variant	Intron 39 of 40	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.5455-13_5455-12delTG		intron_variant	Intron 39 of 40		NP_001397723.1
SBF1	NM_001365819.1	c.5377-13_5377-12delTG		intron_variant	Intron 38 of 39		NP_001352748.1
SBF1	NM_001410795.1	c.5374-13_5374-12delTG		intron_variant	Intron 38 of 39		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8	c.5452-13_5452-12delTG		intron_variant	Intron 39 of 40	1	NM_002972.4	ENSP00000370196.2

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

GnomAD2 exomes AF: 0.437 AC: 108803 AN: 249114 AF XY: 0.431

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 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

African (AFR) AF: 0.159 AC: 5325 AN: 33458

American (AMR) AF: 0.504 AC: 22553 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12629 AN: 26122

East Asian (EAS) AF: 0.744 AC: 29511 AN: 39662

South Asian (SAS) AF: 0.323 AC: 27890 AN: 86222

European-Finnish (FIN) AF: 0.512 AC: 27254 AN: 53216

Middle Eastern (MID) AF: 0.377 AC: 2171 AN: 5754

European-Non Finnish (NFE) AF: 0.402 AC: 446148 AN: 1109864

Other (OTH) AF: 0.406 AC: 24486 AN: 60286

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

African (AFR) AF: 0.175 AC: 7241 AN: 41424

American (AMR) AF: 0.445 AC: 6785 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1643 AN: 3472

East Asian (EAS) AF: 0.776 AC: 3936 AN: 5070

South Asian (SAS) AF: 0.331 AC: 1588 AN: 4804

European-Finnish (FIN) AF: 0.523 AC: 5455 AN: 10440

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28389 AN: 67828

Other (OTH) AF: 0.400 AC: 844 AN: 2110

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

Jul 15, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56853707; hg19: chr22-50885893;