NM_030962.4:c.141+65237G>A

Variant names:

• chr11-10128665-C-T
• rs10734652
• NM_030962.4:c.141+65237G>A

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+65237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,930 control chromosomes in the GnomAD database, including 17,557 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 0.48 (17557 hom., cov: 32)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 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.141+65237G>A		intron	N/A	NP_112224.1
	SBF2	NM_001386339.1		c.141+65237G>A		intron	N/A	NP_001373268.1
	SBF2	NM_001424318.1		c.177+65237G>A		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.141+65237G>A		intron	N/A	ENSP00000256190.8
	SBF2	ENST00000533770.6	TSL:1	c.141+65237G>A		intron	N/A	ENSP00000509247.1
	SBF2	ENST00000526353.2	TSL:1	n.291+65237G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72255 AN: 151810 Hom.: 17526 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.476 AC: 72346 AN: 151930 Hom.: 17557 Cov.: 32 AF XY: 0.479 AC XY: 35598 AN XY: 74244

African (AFR) AF: 0.424 AC: 17561 AN: 41400

American (AMR) AF: 0.571 AC: 8714 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2609 AN: 5160

South Asian (SAS) AF: 0.446 AC: 2143 AN: 4810

European-Finnish (FIN) AF: 0.523 AC: 5518 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33100 AN: 67952

Other (OTH) AF: 0.455 AC: 960 AN: 2108

Alfa AF: 0.492 Hom.: 3196

Bravo AF: 0.478

Asia WGS AF: 0.462 AC: 1601 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Benign	0.18
PhyloP100		0.55
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: rs10734652; hg19: chr11-10150212;