rs145351367

Variant names:

• chr11-9816999-G-A
• rs145351367
• NM_030962.4:c.3819C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS1

The NM_030962.4(SBF2):​c.3819C>T​(p.Ser1273Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.000485 in 1,614,150 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: 5.88
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.147).
• BP6: Variant 11-9816999-G-A is Benign according to our data. Variant chr11-9816999-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 219812.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000302 (46/152288) while in subpopulation NFE AF = 0.000618 (42/68016). AF 95% confidence interval is 0.000469. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.3819C>T	p.Ser1273Ser	synonymous	Exon 29 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.3915C>T	p.Ser1305Ser	synonymous	Exon 30 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.3855C>T	p.Ser1285Ser	synonymous	Exon 30 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.3819C>T	p.Ser1273Ser	synonymous	Exon 29 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.3915C>T	p.Ser1305Ser	synonymous	Exon 30 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.3894C>T	p.Ser1298Ser	synonymous	Exon 30 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251194 AF XY: 0.000214

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000414

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000504 AC: 737 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.000474 AC XY: 345 AN XY: 727234

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000633 AC: 704 AN: 1112002

Other (OTH) AF: 0.000364 AC: 22 AN: 60388

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74474

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000131 AC: 2 AN: 15294

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

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000460 Hom.: 1

Bravo AF: 0.000325

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	1	-	Charcot-Marie-Tooth disease type 4B2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.4
DANN	Benign	0.68
PhyloP100		5.9
Mutation Taster		=96/4	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: rs145351367; hg19: chr11-9838546;