Variant 22-50456591-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002972.4(SBF1):c.3987G>A(p.Ala1329=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,543,372 control chromosomes in the GnomAD database, including 43,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4437 hom., cov: 30)

Exomes 𝑓: 0.22 ( 39330 hom. )

Consequence

SBF1
NM_002972.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

SBF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 22-50456591-C-T is Benign according to our data. Variant chr22-50456591-C-T is described in ClinVar as [Benign]. Clinvar id is 258879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50456591-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SBF1	NM_002972.4 linkuse as main transcript	c.3987G>A	p.Ala1329=	synonymous_variant	30/41	ENST00000380817.8
SBF1	NM_001410794.1 linkuse as main transcript	c.3990G>A	p.Ala1330=	synonymous_variant	30/41
SBF1	NM_001365819.1 linkuse as main transcript	c.3912G>A	p.Ala1304=	synonymous_variant	29/40
SBF1	NM_001410795.1 linkuse as main transcript	c.3909G>A	p.Ala1303=	synonymous_variant	29/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF1	ENST00000380817.8 linkuse as main transcript	c.3987G>A	p.Ala1329=	synonymous_variant	30/41	1	NM_002972.4	P3	O95248-5

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31911

AN:

151890

Hom.:

4441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.285

AC:

45396

AN:

159552

Hom.:

8246

AF XY:

0.277

AC XY:

23801

AN XY:

85898

show subpopulations

Gnomad AFR exome

AF:

0.0967

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.712

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.219

AC:

304539

AN:

1391362

Hom.:

39330

Cov.:

AF XY:

0.219

AC XY:

150160

AN XY:

686146

show subpopulations

Gnomad4 AFR exome

AF:

0.0968

Gnomad4 AMR exome

AF:

0.387

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.225

GnomAD4 genome

AF:

0.210

AC:

31916

AN:

152010

Hom.:

4437

Cov.:

AF XY:

0.217

AC XY:

16158

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.707

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.200

Hom.:

646

Bravo

AF:

0.212

Asia WGS

AF:

0.395

AC:

1367

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Charcot-Marie-Tooth disease type 4B3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

Cadd

Benign

7.6

Dann

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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