11-9956424-T-C

Variant names:

• chr11-9956424-T-C
• rs7106914
• NM_030962.4:c.1860+5533A>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.1860+5533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,042 control chromosomes in the GnomAD database, including 11,637 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 0.38 (11637 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 8 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.1860+5533A>G		intron_variant	Intron 16 of 39	ENST00000256190.13	NP_112224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.1860+5533A>G		intron_variant	Intron 16 of 39	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57619 AN: 151922 Hom.: 11624 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.379 AC: 57671 AN: 152042 Hom.: 11637 Cov.: 32 AF XY: 0.381 AC XY: 28290 AN XY: 74314

African (AFR) AF: 0.264 AC: 10949 AN: 41482

American (AMR) AF: 0.454 AC: 6934 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3464

East Asian (EAS) AF: 0.192 AC: 994 AN: 5188

South Asian (SAS) AF: 0.397 AC: 1910 AN: 4816

European-Finnish (FIN) AF: 0.437 AC: 4606 AN: 10536

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30094 AN: 67954

Other (OTH) AF: 0.350 AC: 740 AN: 2114

Alfa AF: 0.414 Hom.: 2354

Bravo AF: 0.374

Asia WGS AF: 0.279 AC: 970 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		-0.027
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: rs7106914; hg19: chr11-9977971;