rs6484147

Variant names:

• chr11-10273556-T-C
• rs6484147
• NM_030962.4:c.55+20459A>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.55+20459A>G 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 152,080 control chromosomes in the GnomAD database, including 18,713 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 (18713 hom., cov: 32)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.55+20459A>G		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.55+20459A>G		intron_variant	Intron 1 of 39	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74615 AN: 151962 Hom.: 18682 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.491 AC: 74709 AN: 152080 Hom.: 18713 Cov.: 32 AF XY: 0.491 AC XY: 36501 AN XY: 74334

African (AFR) AF: 0.412 AC: 17078 AN: 41484

American (AMR) AF: 0.490 AC: 7500 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1754 AN: 5174

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4816

European-Finnish (FIN) AF: 0.542 AC: 5719 AN: 10554

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

European-Non Finnish (NFE) AF: 0.544 AC: 36960 AN: 67966

Other (OTH) AF: 0.488 AC: 1031 AN: 2112

Alfa AF: 0.505 Hom.: 3471

Bravo AF: 0.479

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		-0.32
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: rs6484147; hg19: chr11-10295103;