rs788018

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012433.4(SF3B1):c.2631T>C(p.Gly877Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,611,526 control chromosomes in the GnomAD database, including 375,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38925 hom., cov: 31)

Exomes 𝑓: 0.68 ( 336277 hom. )

Consequence

SF3B1
NM_012433.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.494

Publications

48 publications found

Variant links:

Genes affected

SF3B1 (HGNC:10768): (splicing factor 3b subunit 1) This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SF3B1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-197400802-A-G is Benign according to our data. Variant chr2-197400802-A-G is described in ClinVar as [Benign]. Clinvar id is 1228123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.494 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B1	NM_012433.4 link	c.2631T>C	p.Gly877Gly	synonymous_variant	Exon 18 of 25	ENST00000335508.11	NP_036565.2	O75533-1B4DGZ4
SF3B1	XM_047443838.1 link	c.2193T>C	p.Gly731Gly	synonymous_variant	Exon 15 of 22		XP_047299794.1
SF3B1	XM_047443839.1 link	c.2193T>C	p.Gly731Gly	synonymous_variant	Exon 15 of 22		XP_047299795.1
SF3B1	XM_047443840.1 link	c.2631T>C	p.Gly877Gly	synonymous_variant	Exon 18 of 22		XP_047299796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B1	ENST00000335508.11 link	c.2631T>C	p.Gly877Gly	synonymous_variant	Exon 18 of 25	1	NM_012433.4	ENSP00000335321.6		O75533-1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107688

AN:

151906

Hom.:

38887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.746

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.746

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.726

GnomAD2 exomes

AF:

0.658

AC:

165154

AN:

251076

AF XY:

0.669

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.750

Gnomad EAS exome

AF:

0.526

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.676

AC:

986349

AN:

1459502

Hom.:

336277

Cov.:

AF XY:

0.679

AC XY:

493158

AN XY:

726262

show subpopulations

African (AFR)

AF:

0.845

AC:

28264

AN:

33442

American (AMR)

AF:

0.517

AC:

23138

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

19484

AN:

26122

East Asian (EAS)

AF:

0.631

AC:

25002

AN:

39644

South Asian (SAS)

AF:

0.755

AC:

65120

AN:

86202

European-Finnish (FIN)

AF:

0.579

AC:

30867

AN:

53282

Middle Eastern (MID)

AF:

0.856

AC:

4927

AN:

5758

European-Non Finnish (NFE)

AF:

0.674

AC:

748214

AN:

1110032

Other (OTH)

AF:

0.685

AC:

41333

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14972

29944

44916

59888

74860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.709

AC:

107780

AN:

152024

Hom.:

38925

Cov.:

AF XY:

0.706

AC XY:

52437

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.834

AC:

34623

AN:

41510

American (AMR)

AF:

0.649

AC:

9889

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

2590

AN:

3470

East Asian (EAS)

AF:

0.549

AC:

2838

AN:

5172

South Asian (SAS)

AF:

0.747

AC:

3601

AN:

4820

European-Finnish (FIN)

AF:

0.571

AC:

6010

AN:

10522

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.674

AC:

45792

AN:

67966

Other (OTH)

AF:

0.725

AC:

1532

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1547

3094

4642

6189

7736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.694

Hom.:

29819

Bravo

AF:

0.716

Asia WGS

AF:

0.652

AC:

2269

AN:

3478

EpiCase

AF:

0.708

EpiControl

AF:

0.709

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SF3B1-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.9

(source)

DANN

Benign

0.77

PhyloP100

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs788018

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over