rs1554909254

Variant names:

• chr11-9816981-A-C
• rs1554909254
• NM_030962.4:c.3837T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_030962.4(SBF2):​c.3837T>G​(p.Ser1279Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.30
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.072).
• BP6: Variant 11-9816981-A-C is Benign according to our data. Variant chr11-9816981-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 543455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.3837T>G	p.Ser1279Ser	synonymous	Exon 29 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.3933T>G	p.Ser1311Ser	synonymous	Exon 30 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.3873T>G	p.Ser1291Ser	synonymous	Exon 30 of 41	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.3837T>G	p.Ser1279Ser	synonymous	Exon 29 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.3933T>G	p.Ser1311Ser	synonymous	Exon 30 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.3912T>G	p.Ser1304Ser	synonymous	Exon 30 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.63
PhyloP100		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1554909254; hg19: chr11-9838528;