Variant 2-197402104-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_012433.4(SF3B1):c.2104C>A(p.Arg702=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00298 in 1,606,010 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 87 hom. )

Consequence

SF3B1
NM_012433.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.13

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 2-197402104-G-T is Benign according to our data. Variant chr2-197402104-G-T is described in ClinVar as [Benign]. Clinvar id is 788088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-197402104-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00661 (1006/152214) while in subpopulation SAS AF= 0.0299 (144/4820). AF 95% confidence interval is 0.0259. There are 13 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1006 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SF3B1	NM_012433.4 linkuse as main transcript	c.2104C>A	p.Arg702=	synonymous_variant	15/25	ENST00000335508.11
SF3B1	XM_047443838.1 linkuse as main transcript	c.1666C>A	p.Arg556=	synonymous_variant	12/22
SF3B1	XM_047443839.1 linkuse as main transcript	c.1666C>A	p.Arg556=	synonymous_variant	12/22
SF3B1	XM_047443840.1 linkuse as main transcript	c.2104C>A	p.Arg702=	synonymous_variant	15/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3B1	ENST00000335508.11 linkuse as main transcript	c.2104C>A	p.Arg702=	synonymous_variant	15/25	1	NM_012433.4	P1	O75533-1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

993

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00560

AC:

1383

AN:

246834

Hom.:

AF XY:

0.00626

AC XY:

837

AN XY:

133602

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.00391

Gnomad SAS exome

AF:

0.0300

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00260

AC:

3776

AN:

1453796

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

2350

AN XY:

722374

show subpopulations

Gnomad4 AFR exome

AF:

0.0195

Gnomad4 AMR exome

AF:

0.000951

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.00362

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00428

GnomAD4 genome

AF:

0.00661

AC:

1006

AN:

152214

Hom.:

Cov.:

AF XY:

0.00713

AC XY:

531

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00386

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00289

Hom.:

Bravo

AF:

0.00676

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.9

DANN

Benign

0.84

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

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