2-197400802-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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:

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=-0.53).

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. Variant chr2-197400802-A-G is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.658

AC:

165154

AN:

251076

Hom.:

55958

AF XY:

0.669

AC XY:

90834

AN XY:

135718

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 SAS exome

AF:

0.757

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

Gnomad4 AFR exome

AF:

0.845

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.746

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.755

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.685

GnomAD4 genome

AF:

0.709

AC:

107780

AN:

152024

Hom.:

38925

Cov.:

AF XY:

0.706

AC XY:

52437

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.834

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.746

Gnomad4 EAS

AF:

0.549

Gnomad4 SAS

AF:

0.747

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.725

Alfa

AF:

0.694

Hom.:

27804

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

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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