rs764823510

Variant names:

• chr11-9787654-C-T
• rs764823510
• NM_030962.4:c.5017G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030962.4(SBF2):​c.5017G>A​(p.Glu1673Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 5.70
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2440702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. 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.5017G>A	p.Glu1673Lys	missense	Exon 36 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.5113G>A	p.Glu1705Lys	missense	Exon 37 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.5053G>A	p.Glu1685Lys	missense	Exon 37 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.5017G>A	p.Glu1673Lys	missense	Exon 36 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.5113G>A	p.Glu1705Lys	missense	Exon 37 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.5092G>A	p.Glu1698Lys	missense	Exon 37 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251476 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111948

Other (OTH) AF: 0.0000331 AC: 2 AN: 60390

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Charcot-Marie-Tooth disease type 4 (1)
-	1	-	Inborn genetic diseases (1)
-	-	-	Congenital thrombocytopenia;C1858278:Charcot-Marie-Tooth disease type 4B2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.39
Sift	Benign	0.34	T
Sift4G	Benign	0.53	T
Polyphen		0.14	B
Vest4		0.57
MVP		0.86
MPC		0.22
ClinPred		0.41	T
GERP RS		6.2
PromoterAI		-0.035	Neutral
Varity_R		0.12
gMVP		0.52
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs764823510; hg19: chr11-9809201;