Variant 22-50447346-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000380817.8(SBF1):c.5559T>C(p.Thr1853=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,434 control chromosomes in the GnomAD database, including 226,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20582 hom., cov: 33)

Exomes 𝑓: 0.53 ( 205494 hom. )

Consequence

SBF1
ENST00000380817.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0790

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 22-50447346-A-G is Benign according to our data. Variant chr22-50447346-A-G is described in ClinVar as [Benign]. Clinvar id is 258881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50447346-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.079 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SBF1	NM_002972.4 linkuse as main transcript	c.5559T>C	p.Thr1853=	synonymous_variant	40/41	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1 linkuse as main transcript	c.5562T>C	p.Thr1854=	synonymous_variant	40/41		NP_001397723.1
SBF1	NM_001365819.1 linkuse as main transcript	c.5484T>C	p.Thr1828=	synonymous_variant	39/40		NP_001352748.1
SBF1	NM_001410795.1 linkuse as main transcript	c.5481T>C	p.Thr1827=	synonymous_variant	39/40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8 linkuse as main transcript	c.5559T>C	p.Thr1853=	synonymous_variant	40/41	1	NM_002972.4	ENSP00000370196	P3	O95248-5

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78909

AN:

151888

Hom.:

20550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.608

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.519

AC:

129468

AN:

249302

Hom.:

33877

AF XY:

0.518

AC XY:

70019

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.545

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.450

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.529

AC:

773485

AN:

1461428

Hom.:

205494

Cov.:

AF XY:

0.528

AC XY:

383667

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.536

Gnomad4 OTH exome

AF:

0.518

GnomAD4 genome

AF:

0.520

AC:

78982

AN:

152006

Hom.:

20582

Cov.:

AF XY:

0.517

AC XY:

38443

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.540

Hom.:

27462

Bravo

AF:

0.522

Asia WGS

AF:

0.417

AC:

1454

AN:

3478

EpiCase

AF:

0.547

EpiControl

AF:

0.548

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

DANN

Benign

0.60

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