rs73410819

Positions:

• chr11-10029748-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 378499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-10029748-C-G is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF2	NM_030962.4	c.513+17G>C		intron_variant		ENST00000256190.13	NP_112224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.513+17G>C		intron_variant		1	NM_030962.4	ENSP00000256190.8

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

GnomAD3 exomes AF: 0.00734 AC: 1843 AN: 251030 Hom.: 18 AF XY: 0.00670 AC XY: 909 AN XY: 135654

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 SAS exome AF: 0.00598

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

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.00389

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00572

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.00433

Gnomad4 OTH exome AF: 0.00661

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

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.00454

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00959 Hom.: 5

Bravo AF: 0.0143

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Charcot-Marie-Tooth disease type 4B2 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Mar 08, 2022	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 06, 2017	- -

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

-

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 08, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs73410819; hg19: chr11-10051295;