NM_030962.4:c.55+20722G>C

Variant names:

• chr11-10273293-C-G
• rs7108358
• NM_030962.4:c.55+20722G>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.55+20722G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,944 control chromosomes in the GnomAD database, including 16,870 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 0.46 (16870 hom., cov: 32)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.55+20722G>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.55+20722G>C		intron_variant	Intron 1 of 39	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69696 AN: 151828 Hom.: 16849 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.459 AC: 69770 AN: 151944 Hom.: 16870 Cov.: 32 AF XY: 0.460 AC XY: 34156 AN XY: 74256

African (AFR) AF: 0.311 AC: 12869 AN: 41430

American (AMR) AF: 0.471 AC: 7189 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3466

East Asian (EAS) AF: 0.338 AC: 1751 AN: 5176

South Asian (SAS) AF: 0.480 AC: 2316 AN: 4824

European-Finnish (FIN) AF: 0.542 AC: 5704 AN: 10522

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36758 AN: 67938

Other (OTH) AF: 0.453 AC: 956 AN: 2110

Alfa AF: 0.488 Hom.: 2304

Bravo AF: 0.442

Asia WGS AF: 0.371 AC: 1290 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.46
PhyloP100		0.10
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: rs7108358; hg19: chr11-10294840;