rs74642088

Positions:

• chr11-9847040-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_030962.4(SBF2):​c.2850C>T​(p.Ile950=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,772 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (65 hom.)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.857

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 11-9847040-G-A is Benign according to our data. Variant chr11-9847040-G-A is described in ClinVar as [Benign]. Clinvar id is 306592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9847040-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF2	NM_030962.4	c.2850C>T	p.Ile950=	synonymous_variant	23/40	ENST00000256190.13	NP_112224.1
LOC101928008	NR_120539.1	n.135+7764G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.2850C>T	p.Ile950=	synonymous_variant	23/40	1	NM_030962.4	ENSP00000256190	P3
	ENST00000533659.1	n.134+7764G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2295 AN: 152134 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00465 AC: 1170 AN: 251344 Hom.: 25 AF XY: 0.00354 AC XY: 481 AN XY: 135846

Gnomad AFR exome AF: 0.0600

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00182 AC: 2660 AN: 1461520 Hom.: 65 Cov.: 31 AF XY: 0.00165 AC XY: 1200 AN XY: 727068

Gnomad4 AFR exome AF: 0.0576

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000240

Gnomad4 OTH exome AF: 0.00392

GnomAD4 genome AF: 0.0151 AC: 2297 AN: 152252 Hom.: 61 Cov.: 32 AF XY: 0.0140 AC XY: 1044 AN XY: 74446

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00707 Hom.: 19

Bravo AF: 0.0176

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000711

ClinVar

Significance: 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	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 08, 2023	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 15, 2020

- -

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

-

- -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.3
DANN	Benign	0.78

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: rs74642088; hg19: chr11-9868587;