NM_030962.4:c.513+17G>C

Variant names:

• chr11-10029748-C-G
• rs73410819
• NM_030962.4:c.513+17G>C

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.513+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,499,248 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (54 hom.)
• Consequence: SBF2 NM_030962.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.04
• 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 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-10029748-C-G is Benign according to our data. Variant chr11-10029748-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378499.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 = 0.0144 (2199/152268) while in subpopulation AFR AF = 0.0374 (1553/41556). AF 95% confidence interval is 0.0358. There are 38 homozygotes in GnomAd4. There are 1124 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 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.513+17G>C		intron	N/A	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.513+17G>C		intron	N/A	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.549+17G>C		intron	N/A	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.513+17G>C		intron	N/A	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.513+17G>C		intron	N/A	ENSP00000509247.1	Q86WG5-3
	SBF2	ENST00000526353.2	TSL:1	n.663+17G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2194 AN: 152150 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00454

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00734 AC: 1843 AN: 251030 AF XY: 0.00670

Gnomad AFR exome AF: 0.0375

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0178

Gnomad NFE exome AF: 0.00454

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00561 AC: 7559 AN: 1346980 Hom.: 54 Cov.: 23 AF XY: 0.00546 AC XY: 3698 AN XY: 676756

African (AFR) AF: 0.0379 AC: 1176 AN: 31066

American (AMR) AF: 0.00298 AC: 133 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00389 AC: 99 AN: 25448

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39122

South Asian (SAS) AF: 0.00572 AC: 480 AN: 83902

European-Finnish (FIN) AF: 0.0164 AC: 875 AN: 53372

Middle Eastern (MID) AF: 0.0101 AC: 56 AN: 5520

European-Non Finnish (NFE) AF: 0.00433 AC: 4365 AN: 1007390

Other (OTH) AF: 0.00661 AC: 374 AN: 56578

GnomAD4 genome AF: 0.0144 AC: 2199 AN: 152268 Hom.: 38 Cov.: 32 AF XY: 0.0151 AC XY: 1124 AN XY: 74438

African (AFR) AF: 0.0374 AC: 1553 AN: 41556

American (AMR) AF: 0.00549 AC: 84 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.0172 AC: 182 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00454 AC: 309 AN: 68014

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00959 Hom.: 5

Bravo AF: 0.0143

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs73410819; hg19: chr11-10051295;