NM_030962.4:c.4693A>G

Variant names:

• chr11-9790561-T-C
• rs115345208
• NM_030962.4:c.4693A>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.4693A>G​(p.Ile1565Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,583,982 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.20
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069927275).
• BP6: Variant 11-9790561-T-C is Benign according to our data. Variant chr11-9790561-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00264 (402/152326) while in subpopulation AFR AF = 0.00912 (379/41574). AF 95% confidence interval is 0.00836. There are 2 homozygotes in GnomAd4. There are 184 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.4693A>G	p.Ile1565Val	missense	Exon 34 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.4789A>G	p.Ile1597Val	missense	Exon 35 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.4729A>G	p.Ile1577Val	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.4693A>G	p.Ile1565Val	missense	Exon 34 of 40	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.4789A>G	p.Ile1597Val	missense	Exon 35 of 41	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.4768A>G	p.Ile1590Val	missense	Exon 35 of 41	ENSP00000502491.1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 401 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000788 AC: 193 AN: 244936 AF XY: 0.000636

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.000480

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000250 AC: 358 AN: 1431656 Hom.: 2 Cov.: 27 AF XY: 0.000217 AC XY: 155 AN XY: 713046

African (AFR) AF: 0.00820 AC: 268 AN: 32682

American (AMR) AF: 0.000576 AC: 25 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.0000241 AC: 2 AN: 83156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5688

European-Non Finnish (NFE) AF: 0.0000248 AC: 27 AN: 1088748

Other (OTH) AF: 0.000589 AC: 35 AN: 59400

GnomAD4 genome AF: 0.00264 AC: 402 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00247 AC XY: 184 AN XY: 74502

African (AFR) AF: 0.00912 AC: 379 AN: 41574

American (AMR) AF: 0.00118 AC: 18 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.000933 Hom.: 2

Bravo AF: 0.00317

ESP6500AA AF: 0.00795 AC: 35

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000981 AC: 119

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.72	N
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.13
Sift	Benign	0.33	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.71
MPC		0.15
ClinPred		0.0043	T
GERP RS		3.7
Varity_R		0.032
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs115345208; hg19: chr11-9812108;