Variant 2-197393071-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012433.4(SF3B1):c.3657A>G(p.Val1219=) 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 1,611,676 control chromosomes in the GnomAD database, including 375,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39045 hom., cov: 32)

Exomes 𝑓: 0.68 ( 336168 hom. )

Consequence

SF3B1
NM_012433.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.231

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-197393071-T-C is Benign according to our data. Variant chr2-197393071-T-C is described in ClinVar as [Benign]. Clinvar id is 1250652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-197393071-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.231 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SF3B1	NM_012433.4 linkuse as main transcript	c.3657A>G	p.Val1219=	synonymous_variant	24/25	ENST00000335508.11
SF3B1	XM_047443838.1 linkuse as main transcript	c.3219A>G	p.Val1073=	synonymous_variant	21/22
SF3B1	XM_047443839.1 linkuse as main transcript	c.3219A>G	p.Val1073=	synonymous_variant	21/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3B1	ENST00000335508.11 linkuse as main transcript	c.3657A>G	p.Val1219=	synonymous_variant	24/25	1	NM_012433.4	P1	O75533-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107863

AN:

151992

Hom.:

39007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.727

GnomAD3 exomes

AF:

0.658

AC:

165437

AN:

251276

Hom.:

56094

AF XY:

0.670

AC XY:

90958

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.840

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.753

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.676

AC:

986242

AN:

1459566

Hom.:

336168

Cov.:

AF XY:

0.679

AC XY:

493024

AN XY:

726240

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.755

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.686

GnomAD4 genome

AF:

0.710

AC:

107954

AN:

152110

Hom.:

39045

Cov.:

AF XY:

0.706

AC XY:

52531

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.836

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.750

Gnomad4 EAS

AF:

0.554

Gnomad4 SAS

AF:

0.748

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.727

Alfa

AF:

0.690

Hom.:

19655

Bravo

AF:

0.717

Asia WGS

AF:

0.655

AC:

2280

AN:

3478

EpiCase

AF:

0.707

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 05, 2019	- -

SF3B1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

-0.46

CADD

Benign

8.5

DANN

Benign

0.78

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