rs16907355

Variant names:

• chr11-9998332-G-A
• rs16907355
• NM_030962.4:c.909C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_030962.4(SBF2):​c.909C>T​(p.Pro303Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 1,606,236 control chromosomes in the GnomAD database, including 4,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (358 hom., cov: 33)
  • Exomes 𝑓: 0.069 (4416 hom.)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.923
• Publications: 10 publications found

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ENSG00000286561 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-9998332-G-A is Benign according to our data. Variant chr11-9998332-G-A is described in ClinVar as Benign. ClinVar VariationId is 138963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.923 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.909C>T	p.Pro303Pro	synonymous	Exon 9 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.909C>T	p.Pro303Pro	synonymous	Exon 9 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.945C>T	p.Pro315Pro	synonymous	Exon 10 of 41	NP_001411247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.909C>T	p.Pro303Pro	synonymous	Exon 9 of 40	ENSP00000256190.8
	SBF2	ENST00000533770.6	TSL:1	c.909C>T	p.Pro303Pro	synonymous	Exon 9 of 26	ENSP00000509247.1
	SBF2	ENST00000526353.2	TSL:1	n.1059C>T		non_coding_transcript_exon	Exon 9 of 16

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9325 AN: 152054 Hom.: 356 Cov.: 33

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0718

GnomAD2 exomes AF: 0.0740 AC: 18560 AN: 250760 AF XY: 0.0812

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.0387

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0246

Gnomad FIN exome AF: 0.0639

Gnomad NFE exome AF: 0.0741

Gnomad OTH exome AF: 0.0829

GnomAD4 exome AF: 0.0693 AC: 100780 AN: 1454062 Hom.: 4416 Cov.: 29 AF XY: 0.0729 AC XY: 52726 AN XY: 723728

African (AFR) AF: 0.0362 AC: 1209 AN: 33358

American (AMR) AF: 0.0405 AC: 1807 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3384 AN: 26036

East Asian (EAS) AF: 0.0227 AC: 898 AN: 39606

South Asian (SAS) AF: 0.149 AC: 12779 AN: 85810

European-Finnish (FIN) AF: 0.0618 AC: 3295 AN: 53280

Middle Eastern (MID) AF: 0.187 AC: 1073 AN: 5724

European-Non Finnish (NFE) AF: 0.0649 AC: 71748 AN: 1105488

Other (OTH) AF: 0.0763 AC: 4587 AN: 60106

GnomAD4 genome AF: 0.0614 AC: 9342 AN: 152174 Hom.: 358 Cov.: 33 AF XY: 0.0620 AC XY: 4610 AN XY: 74404

African (AFR) AF: 0.0364 AC: 1513 AN: 41530

American (AMR) AF: 0.0502 AC: 767 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3468

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5174

South Asian (SAS) AF: 0.141 AC: 680 AN: 4824

European-Finnish (FIN) AF: 0.0613 AC: 649 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4766 AN: 67982

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0696 Hom.: 1360

Bravo AF: 0.0573

Asia WGS AF: 0.0780 AC: 271 AN: 3478

EpiCase AF: 0.0813

EpiControl AF: 0.0811

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 12, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Charcot-Marie-Tooth disease Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease type 4B2 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Charcot-Marie-Tooth disease type 4 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		0.92
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs16907355; hg19: chr11-10019879; COSMIC: COSV56300255;