chr11-9787654-CTTT-C

Variant names:

• chr11-9787654-CTTT-C
• rs750958357
• NM_030962.4:c.5014_5016delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_Supporting BS1_Supporting

The NM_030962.4(SBF2):​c.5014_5016delAAA​(p.Lys1672del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000444 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. K1672K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (0 hom.)
• Consequence: SBF2 NM_030962.4 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:9
• Conservation: PhyloP100: 5.72
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_030962.4. Strenght limited to Supporting due to length of the change: 1aa.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00063 (96/152316) while in subpopulation AMR AF = 0.0017 (26/15310). AF 95% confidence interval is 0.00119. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.5014_5016delAAA	p.Lys1672del	conservative_inframe_deletion	Exon 36 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.5110_5112delAAA	p.Lys1704del	conservative_inframe_deletion	Exon 37 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.5050_5052delAAA	p.Lys1684del	conservative_inframe_deletion	Exon 37 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.5014_5016delAAA	p.Lys1672del	conservative_inframe_deletion	Exon 36 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.5110_5112delAAA	p.Lys1704del	conservative_inframe_deletion	Exon 37 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.5089_5091delAAA	p.Lys1697del	conservative_inframe_deletion	Exon 37 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000457 AC: 115 AN: 251476 AF XY: 0.000544

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000589

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000424 AC: 620 AN: 1461818 Hom.: 0 AF XY: 0.000446 AC XY: 324 AN XY: 727214

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

American (AMR) AF: 0.000514 AC: 23 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000453 AC: 504 AN: 1111946

Other (OTH) AF: 0.000381 AC: 23 AN: 60390

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000671 AC XY: 50 AN XY: 74478

African (AFR) AF: 0.000217 AC: 9 AN: 41568

American (AMR) AF: 0.00170 AC: 26 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68030

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.000737

EpiCase AF: 0.000600

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7
Mutation Taster		=73/27	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: rs750958357; hg19: chr11-9809201;