NM_030962.4:c.909C>T

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Charcot-Marie-Tooth disease type 4B2 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

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;