NM_030962.4:c.2035G>A

Variant names:

• chr11-9858291-C-T
• rs7102464
• NM_030962.4:c.2035G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030962.4(SBF2):​c.2035G>A​(p.Glu679Lys) variant causes a missense change. The variant allele was found at a frequency of 0.102 in 1,613,964 control chromosomes in the GnomAD database, including 10,111 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (779 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9332 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.00
• Publications: 29 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=0.001321584).
• BP6: Variant 11-9858291-C-T is Benign according to our data. Variant chr11-9858291-C-T is described in ClinVar as Benign. ClinVar VariationId is 306602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

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.2035G>A	p.Glu679Lys	missense	Exon 18 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.2035G>A	p.Glu679Lys	missense	Exon 18 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.2071G>A	p.Glu691Lys	missense	Exon 19 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.2035G>A	p.Glu679Lys	missense	Exon 18 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.2035G>A	p.Glu679Lys	missense	Exon 18 of 26	ENSP00000509247.1	Q86WG5-3
	ENSG00000255476	ENST00000533659.1	TSL:1	n.134+19015C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12158 AN: 152108 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0597

GnomAD2 exomes AF: 0.0767 AC: 19291 AN: 251452 AF XY: 0.0759

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.0382

Gnomad ASJ exome AF: 0.0359

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0735

GnomAD4 exome AF: 0.104 AC: 151753 AN: 1461740 Hom.: 9332 Cov.: 32 AF XY: 0.101 AC XY: 73497 AN XY: 727178

African (AFR) AF: 0.0143 AC: 480 AN: 33480

American (AMR) AF: 0.0408 AC: 1825 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 1024 AN: 26132

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0140 AC: 1208 AN: 86258

European-Finnish (FIN) AF: 0.190 AC: 10169 AN: 53418

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.118 AC: 131623 AN: 1111870

Other (OTH) AF: 0.0888 AC: 5365 AN: 60392

GnomAD4 genome AF: 0.0799 AC: 12158 AN: 152224 Hom.: 779 Cov.: 32 AF XY: 0.0818 AC XY: 6085 AN XY: 74406

African (AFR) AF: 0.0197 AC: 817 AN: 41544

American (AMR) AF: 0.0628 AC: 961 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2194 AN: 10580

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7851 AN: 68004

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0927 Hom.: 2596

Bravo AF: 0.0660

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.120 AC: 464

ESP6500AA AF: 0.0232 AC: 102

ESP6500EA AF: 0.107 AC: 918

ExAC AF: 0.0751 AC: 9122

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.0982

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Charcot-Marie-Tooth disease type 4B2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	26
DANN	Benign	0.90
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.095
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.12
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.058
MPC		0.20
ClinPred		0.019	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.17
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7102464; hg19: chr11-9879838; COSMIC: COSV56293147;