11-10138336-T-C

Variant names:

• chr11-10138336-T-C
• rs4323860
• NM_030962.4:c.141+55566A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030962.4(SBF2):​c.141+55566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,828 control chromosomes in the GnomAD database, including 19,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19121 hom., cov: 31)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.141+55566A>G		intron	N/A	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.141+55566A>G		intron	N/A	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.177+55566A>G		intron	N/A	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.141+55566A>G		intron	N/A	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.141+55566A>G		intron	N/A	ENSP00000509247.1	Q86WG5-3
	SBF2	ENST00000526353.2	TSL:1	n.291+55566A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75462 AN: 151708 Hom.: 19088 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75558 AN: 151828 Hom.: 19121 Cov.: 31 AF XY: 0.498 AC XY: 36914 AN XY: 74178

African (AFR) AF: 0.430 AC: 17823 AN: 41408

American (AMR) AF: 0.491 AC: 7493 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1802 AN: 3464

East Asian (EAS) AF: 0.341 AC: 1757 AN: 5160

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4818

European-Finnish (FIN) AF: 0.557 AC: 5857 AN: 10516

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36885 AN: 67898

Other (OTH) AF: 0.486 AC: 1024 AN: 2108

Alfa AF: 0.401 Hom.: 1330

Bravo AF: 0.484

Asia WGS AF: 0.391 AC: 1356 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.41
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs4323860; hg19: chr11-10159883;