11-9992538-T-C

Position:

chr11-9992538-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_030962.4(SBF2):c.1173A>G(p.Ala391Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,610,934 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 108 hom. )

Consequence

SBF2
NM_030962.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.80

Variant links:

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 links:

SBF2 (HGNC:):

SBF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 11-9992538-T-C is Benign according to our data. Variant chr11-9992538-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 220575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9992538-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00725 (1103/152182) while in subpopulation SAS AF= 0.0131 (63/4820). AF 95% confidence interval is 0.0105. There are 9 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF2	NM_030962.4 linkuse as main transcript	c.1173A>G	p.Ala391Ala	synonymous_variant	12/40	ENST00000256190.13	NP_112224.1	Q86WG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13 linkuse as main transcript	c.1173A>G	p.Ala391Ala	synonymous_variant	12/40	1	NM_030962.4	ENSP00000256190.8		Q86WG5-1

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1102

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00623

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.00359

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00751

AC:

1870

AN:

249112

Hom.:

AF XY:

0.00828

AC XY:

1115

AN XY:

134626

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.00830

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00954

Gnomad OTH exome

AF:

0.00938

GnomAD4 exome

AF:

0.00909

AC:

13256

AN:

1458752

Hom.:

108

Cov.:

AF XY:

0.00941

AC XY:

6828

AN XY:

725494

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.00488

Gnomad4 ASJ exome

AF:

0.00745

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00414

Gnomad4 NFE exome

AF:

0.00947

Gnomad4 OTH exome

AF:

0.00959

GnomAD4 genome

AF:

0.00725

AC:

1103

AN:

152182

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

509

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00623

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00359

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00864

Hom.:

Bravo

AF:

0.00725

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ENSG00000286561: BS1, BS2; SBF2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 02, 2017	- -

Charcot-Marie-Tooth disease type 4B2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Oct 26, 2023	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over