rs16907355

chr11-9998332-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_030962.4(SBF2):c.909C>T(p.Pro303=) 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:4
• Conservation: PhyloP100: 0.923

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 138963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9998332-G-A is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBF2	NM_030962.4	c.909C>T	p.Pro303=	synonymous_variant	9/40	ENST00000256190.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13	c.909C>T	p.Pro303=	synonymous_variant	9/40	1	NM_030962.4	P3
	ENST00000667219.1	n.252-354G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0740 AC: 18560 AN: 250760 Hom.: 968 AF XY: 0.0812 AC XY: 11002 AN XY: 135508

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 SAS exome AF: 0.152

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

Gnomad4 AFR exome AF: 0.0362

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0618

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0763

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

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0613

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0715

Alfa AF: 0.0726 Hom.: 729

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

-

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2014

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 type 4B2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs16907355; hg19: chr11-10019879; COSMIC: COSV56300255;