11-10266441-G-A

Variant names:

• chr11-10266441-G-A
• rs11042702
• NM_030962.4:c.55+27574C>T

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+27574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,940 control chromosomes in the GnomAD database, including 18,822 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 (18822 hom., cov: 32)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.55+27574C>T		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+27574C>T		intron_variant	Intron 1 of 39	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74757 AN: 151820 Hom.: 18790 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.555

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: 0.493 AC: 74854 AN: 151940 Hom.: 18822 Cov.: 32 AF XY: 0.493 AC XY: 36620 AN XY: 74254

African (AFR) AF: 0.413 AC: 17095 AN: 41432

American (AMR) AF: 0.490 AC: 7490 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1809 AN: 3464

East Asian (EAS) AF: 0.338 AC: 1746 AN: 5164

South Asian (SAS) AF: 0.482 AC: 2320 AN: 4814

European-Finnish (FIN) AF: 0.555 AC: 5863 AN: 10556

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

European-Non Finnish (NFE) AF: 0.544 AC: 36962 AN: 67926

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

Alfa AF: 0.523 Hom.: 11748

Bravo AF: 0.479

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.1
DANN	Benign	0.35
PhyloP100		0.56
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: rs11042702; hg19: chr11-10287988;