rs563878786

Variant names:

• chr11-9790567-A-C
• rs563878786
• NM_030962.4:c.4687T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-9790567-A-C
• chr11-9790567-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001386339.1(SBF2):​c.4783T>G​(p.Leu1595Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1595L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SBF2 NM_001386339.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 0 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-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

LOC105369149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045089692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386339.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.4687T>G	p.Leu1563Val	missense	Exon 34 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.4783T>G	p.Leu1595Val	missense	Exon 35 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.4723T>G	p.Leu1575Val	missense	Exon 35 of 41	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.4687T>G	p.Leu1563Val	missense	Exon 34 of 40	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.4783T>G	p.Leu1595Val	missense	Exon 35 of 41	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.4762T>G	p.Leu1588Val	missense	Exon 35 of 41	ENSP00000502491.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432088 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 713422

African (AFR) AF: 0.00 AC: 0 AN: 32724

American (AMR) AF: 0.00 AC: 0 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.00 AC: 0 AN: 83454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088540

Other (OTH) AF: 0.00 AC: 0 AN: 59412

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.1
DANN	Benign	0.83
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.030	N
PhyloP100		-0.97
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.20
Sift	Benign	0.30	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.38		Gain of phosphorylation at Y1560 (P = 0.1562)
MVP		0.36
MPC		0.18
ClinPred		0.035	T
GERP RS		-2.5
Varity_R		0.045
gMVP		0.29
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs563878786; hg19: chr11-9812114;