NM_030962.4:c.55+13546G>A

Variant names:

• chr11-10280469-C-T
• rs10500724
• NM_030962.4:c.55+13546G>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.55+13546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,894 control chromosomes in the GnomAD database, including 18,668 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 0.49 (18668 hom., cov: 31)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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: 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=-0.96).
• 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.55+13546G>A		intron	N/A	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.55+13546G>A		intron	N/A	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.91+19937G>A		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.55+13546G>A		intron	N/A	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.55+13546G>A		intron	N/A	ENSP00000509247.1	Q86WG5-3
	SBF2	ENST00000526353.2	TSL:1	n.205+13546G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74502 AN: 151776 Hom.: 18639 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.491 AC: 74595 AN: 151894 Hom.: 18668 Cov.: 31 AF XY: 0.491 AC XY: 36443 AN XY: 74228

African (AFR) AF: 0.412 AC: 17063 AN: 41416

American (AMR) AF: 0.490 AC: 7477 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1812 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1730 AN: 5172

South Asian (SAS) AF: 0.480 AC: 2308 AN: 4810

European-Finnish (FIN) AF: 0.542 AC: 5706 AN: 10526

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36935 AN: 67932

Other (OTH) AF: 0.486 AC: 1025 AN: 2108

Alfa AF: 0.395 Hom.: 1254

Bravo AF: 0.478

Asia WGS AF: 0.378 AC: 1313 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	0.19
DANN	Benign	0.21
PhyloP100		-1.6
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: rs10500724; hg19: chr11-10302016;