dbSNP rs1554975593: SBF2:c.1297-6T>C (chr11-9989601-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_030962.4(SBF2):c.1297-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

SBF2
NM_030962.4 splice_region, intron

Scores

Splicing: ADA: 0.0001276

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.34

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4B2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

SBF2 links:

ENSG00000286561 (HGNC:):

ENSG00000286561 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 11-9989601-A-G is Benign according to our data. Variant chr11-9989601-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 543437.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SBF2	NM_030962.4	MANE Select	c.1297-6T>C	splice_region intron	N/A	NP_112224.1
SBF2	NM_001386339.1		c.1297-6T>C	splice_region intron	N/A	NP_001373268.1
SBF2	NM_001424318.1		c.1333-6T>C	splice_region intron	N/A	NP_001411247.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SBF2	ENST00000256190.13	TSL:1 MANE Select	c.1297-6T>C	splice_region intron	N/A	ENSP00000256190.8
SBF2	ENST00000533770.6	TSL:1	c.1297-6T>C	splice_region intron	N/A	ENSP00000509247.1
SBF2	ENST00000526353.2	TSL:1	n.1447-6T>C	splice_region intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.37e-7

AC:

AN:

1357332

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31332

American (AMR)

AF:

0.00

AC:

AN:

43460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25308

East Asian (EAS)

AF:

0.00

AC:

AN:

39110

South Asian (SAS)

AF:

0.00

AC:

AN:

81790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

9.79e-7

AC:

AN:

1021248

Other (OTH)

AF:

0.00

AC:

AN:

56846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4

Benign:1

Dec 17, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

3.3

PromoterAI

0.0014

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.034

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over