rs1372809

Variant names:

• chr11-10222558-C-G
• rs1372809
• NM_030962.4:c.56-28571G>C

Variant summary

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

The NM_030962.4(SBF2):​c.56-28571G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,988 control chromosomes in the GnomAD database, including 12,827 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 0.39 (12827 hom., cov: 31)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.56-28571G>C		intron_variant	Intron 1 of 39	ENST00000256190.13	NP_112224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.56-28571G>C		intron_variant	Intron 1 of 39	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59734 AN: 151870 Hom.: 12807 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.393 AC: 59801 AN: 151988 Hom.: 12827 Cov.: 31 AF XY: 0.394 AC XY: 29278 AN XY: 74282

African (AFR) AF: 0.268 AC: 11096 AN: 41436

American (AMR) AF: 0.358 AC: 5465 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3470

East Asian (EAS) AF: 0.0545 AC: 282 AN: 5178

South Asian (SAS) AF: 0.428 AC: 2065 AN: 4822

European-Finnish (FIN) AF: 0.510 AC: 5382 AN: 10560

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32735 AN: 67942

Other (OTH) AF: 0.383 AC: 805 AN: 2104

Alfa AF: 0.439 Hom.: 1919

Bravo AF: 0.369

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.74
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: rs1372809; hg19: chr11-10244105; COSMIC: COSV56312698;