chr11-9830928-G-A

Variant names:

• chr11-9830928-G-A
• rs2403221
• NM_030962.4:c.3652+1296C>T

Variant summary

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

The NM_001386339.1(SBF2):​c.3652+1296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,960 control chromosomes in the GnomAD database, including 22,731 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 0.51 (22731 hom., cov: 32)
• Consequence: SBF2 NM_001386339.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 6 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386339.1. 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.3652+1296C>T		intron	N/A	NP_112224.1
	SBF2	NM_001386339.1		c.3652+1296C>T		intron	N/A	NP_001373268.1
	SBF2	NM_001424318.1		c.3688+1296C>T		intron	N/A	NP_001411247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.3652+1296C>T		intron	N/A	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.3652+1296C>T		intron	N/A	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.3652+1296C>T		intron	N/A	ENSP00000502491.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78190 AN: 151842 Hom.: 22726 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.515 AC: 78208 AN: 151960 Hom.: 22731 Cov.: 32 AF XY: 0.512 AC XY: 38048 AN XY: 74284

African (AFR) AF: 0.286 AC: 11867 AN: 41432

American (AMR) AF: 0.487 AC: 7445 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3472

East Asian (EAS) AF: 0.156 AC: 806 AN: 5176

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4824

European-Finnish (FIN) AF: 0.692 AC: 7272 AN: 10508

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45045 AN: 67956

Other (OTH) AF: 0.499 AC: 1055 AN: 2114

Alfa AF: 0.608 Hom.: 15702

Bravo AF: 0.484

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-0.11
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: rs2403221; hg19: chr11-9852475;