11-9839661-G-C

Variant names:

• chr11-9839661-G-C
• rs117957652
• NM_030962.4:c.3292C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030962.4(SBF2):​c.3292C>G​(p.Leu1098Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,614,040 control chromosomes in the GnomAD database, including 476 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1098L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.018 (32 hom., cov: 32)
  • Exomes 𝑓: 0.023 (444 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.404
• Publications: 19 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P, Orphanet

ENSG00000255476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005821973).
• BP6: Variant 11-9839661-G-C is Benign according to our data. Variant chr11-9839661-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0177 (2696/152264) while in subpopulation NFE AF = 0.0262 (1780/68022). AF 95% confidence interval is 0.0252. There are 32 homozygotes in GnomAd4. There are 1272 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

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.3292C>G	p.Leu1098Val	missense	Exon 26 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.3292C>G	p.Leu1098Val	missense	Exon 26 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.3328C>G	p.Leu1110Val	missense	Exon 27 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.3292C>G	p.Leu1098Val	missense	Exon 26 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.3292C>G	p.Leu1098Val	missense	Exon 26 of 26	ENSP00000509247.1	Q86WG5-3
	ENSG00000255476	ENST00000533659.1	TSL:1	n.134+385G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2698 AN: 152146 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00420

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.0204 AC: 5136 AN: 251482 AF XY: 0.0214

Gnomad AFR exome AF: 0.00332

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0226 AC: 33052 AN: 1461776 Hom.: 444 Cov.: 33 AF XY: 0.0231 AC XY: 16787 AN XY: 727190

African (AFR) AF: 0.00346 AC: 116 AN: 33478

American (AMR) AF: 0.0140 AC: 624 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 912 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0233 AC: 2013 AN: 86252

European-Finnish (FIN) AF: 0.0203 AC: 1085 AN: 53414

Middle Eastern (MID) AF: 0.0284 AC: 164 AN: 5768

European-Non Finnish (NFE) AF: 0.0242 AC: 26874 AN: 1111908

Other (OTH) AF: 0.0209 AC: 1261 AN: 60396

GnomAD4 genome AF: 0.0177 AC: 2696 AN: 152264 Hom.: 32 Cov.: 32 AF XY: 0.0171 AC XY: 1272 AN XY: 74454

African (AFR) AF: 0.00419 AC: 174 AN: 41542

American (AMR) AF: 0.0156 AC: 239 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4816

European-Finnish (FIN) AF: 0.0177 AC: 188 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1780 AN: 68022

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0226 Hom.: 37

Bravo AF: 0.0171

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0221 AC: 85

ESP6500AA AF: 0.00454 AC: 20

ESP6500EA AF: 0.0298 AC: 256

ExAC AF: 0.0209 AC: 2539

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Charcot-Marie-Tooth disease type 4B2 (3)
-	-	3	not specified (3)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.40
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.067
Sift	Benign	0.89	T
Sift4G	Benign	0.79	T
Polyphen		0.87	P
Vest4		0.49
MPC		0.19
ClinPred		0.013	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.33
Mutation Taster		=78/22	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: rs117957652; hg19: chr11-9861208; COSMIC: COSV108003722; COSMIC: COSV108003722;