rs2645029

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030962.4(SBF2):c.4571-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,566,904 control chromosomes in the GnomAD database, including 605,599 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58356 hom., cov: 32)

Exomes 𝑓: 0.88 ( 547243 hom. )

Consequence

SBF2
NM_030962.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001848

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.842

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-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

SBF2-AS1 links:

LOC105369149 (HGNC:):

LOC105369149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-9790689-G-A is Benign according to our data. Variant chr11-9790689-G-A is described in ClinVar as [Benign]. Clinvar id is 261940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9790689-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SBF2	NM_030962.4 linkuse as main transcript	c.4571-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000256190.13	NP_112224.1
SBF2-AS1	NR_036485.1 linkuse as main transcript	n.212-17159G>A	intron_variant, non_coding_transcript_variant
LOC105369149	XR_007062587.1 linkuse as main transcript	n.356-180G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13 linkuse as main transcript	c.4571-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030962.4	ENSP00000256190	P3	Q86WG5-1
SBF2-AS1	ENST00000663578.1 linkuse as main transcript	n.237-17159G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

132911

AN:

152120

Hom.:

58327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.885

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.953

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.894

Gnomad OTH

AF:

0.862

GnomAD3 exomes

AF:

0.861

AC:

210536

AN:

244590

Hom.:

91352

AF XY:

0.858

AC XY:

113616

AN XY:

132430

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.865

Gnomad ASJ exome

AF:

0.914

Gnomad EAS exome

AF:

0.686

Gnomad SAS exome

AF:

0.753

Gnomad FIN exome

AF:

0.948

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.876

GnomAD4 exome

AF:

0.878

AC:

1241731

AN:

1414666

Hom.:

547243

Cov.:

AF XY:

0.875

AC XY:

617068

AN XY:

705514

show subpopulations

Gnomad4 AFR exome

AF:

0.850

Gnomad4 AMR exome

AF:

0.867

Gnomad4 ASJ exome

AF:

0.910

Gnomad4 EAS exome

AF:

0.684

Gnomad4 SAS exome

AF:

0.757

Gnomad4 FIN exome

AF:

0.946

Gnomad4 NFE exome

AF:

0.892

Gnomad4 OTH exome

AF:

0.860

GnomAD4 genome

AF:

0.874

AC:

132993

AN:

152238

Hom.:

58356

Cov.:

AF XY:

0.872

AC XY:

64946

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.854

Gnomad4 AMR

AF:

0.880

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.741

Gnomad4 FIN

AF:

0.953

Gnomad4 NFE

AF:

0.894

Gnomad4 OTH

AF:

0.859

Alfa

AF:

0.887

Hom.:

27390

Bravo

AF:

0.868

Asia WGS

AF:

0.693

AC:

2411

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2017	- -

Charcot-Marie-Tooth disease type 4B2

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	Genome-Nilou Lab	Nov 07, 2021	- -

not provided

Benign:2

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

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

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