chr11-10039876-T-C

Variant names:

• chr11-10039876-T-C
• rs7938647
• NM_030962.4:c.279+2968A>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.279+2968A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,620 control chromosomes in the GnomAD database, including 3,975 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 0.20 (3975 hom., cov: 31)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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.279+2968A>G		intron	N/A	NP_112224.1
	SBF2	NM_001386339.1		c.279+2968A>G		intron	N/A	NP_001373268.1
	SBF2	NM_001424318.1		c.315+2968A>G		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.279+2968A>G		intron	N/A	ENSP00000256190.8
	SBF2	ENST00000533770.6	TSL:1	c.279+2968A>G		intron	N/A	ENSP00000509247.1
	SBF2	ENST00000526353.2	TSL:1	n.429+2968A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30591 AN: 151502 Hom.: 3972 Cov.: 31

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.202 AC: 30604 AN: 151620 Hom.: 3975 Cov.: 31 AF XY: 0.199 AC XY: 14731 AN XY: 74144

African (AFR) AF: 0.0602 AC: 2497 AN: 41446

American (AMR) AF: 0.216 AC: 3285 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3460

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5176

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2318 AN: 10526

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20197 AN: 67670

Other (OTH) AF: 0.177 AC: 373 AN: 2106

Alfa AF: 0.276 Hom.: 5037

Bravo AF: 0.191

Asia WGS AF: 0.0780 AC: 271 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.86
PhyloP100		-0.17
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: rs7938647; hg19: chr11-10061423;