2-197398035-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BS1BS2

The NM_012433.4(SF3B1):c.3216T>C(p.Ala1072Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,613,462 control chromosomes in the GnomAD database, including 49 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 46 hom. )

Consequence

SF3B1
NM_012433.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.86

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 2-197398035-A-G is Benign according to our data. Variant chr2-197398035-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 715640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.86 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00457 (696/152312) while in subpopulation NFE AF = 0.00784 (533/68024). AF 95% confidence interval is 0.00729. There are 3 homozygotes in GnomAd4. There are 314 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 696 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B1	NM_012433.4 link	c.3216T>C	p.Ala1072Ala	synonymous_variant	Exon 22 of 25	ENST00000335508.11	NP_036565.2	O75533-1B4DGZ4
SF3B1	XM_047443838.1 link	c.2778T>C	p.Ala926Ala	synonymous_variant	Exon 19 of 22		XP_047299794.1
SF3B1	XM_047443839.1 link	c.2778T>C	p.Ala926Ala	synonymous_variant	Exon 19 of 22		XP_047299795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B1	ENST00000335508.11 link	c.3216T>C	p.Ala1072Ala	synonymous_variant	Exon 22 of 25	1	NM_012433.4	ENSP00000335321.6		O75533-1

Frequencies

GnomAD3 genomes

AF:

0.00457

AC:

696

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00783

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00469

AC:

1179

AN:

251384

AF XY:

0.00497

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00688

AC:

10047

AN:

1461150

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

4972

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33468

American (AMR)

AF:

0.00177

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39668

South Asian (SAS)

AF:

0.00525

AC:

453

AN:

86236

European-Finnish (FIN)

AF:

0.00316

AC:

169

AN:

53404

Middle Eastern (MID)

AF:

0.00659

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00799

AC:

8882

AN:

1111398

Other (OTH)

AF:

0.00558

AC:

337

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

445

890

1336

1781

2226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152312

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41570

American (AMR)

AF:

0.00281

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00560

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00784

AC:

533

AN:

68024

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.00433

Asia WGS

AF:

0.000578

AC:

AN:

3474

EpiCase

AF:

0.00611

EpiControl

AF:

0.00640

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SF3B1: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

2.9

Mutation Taster

=87/13

polymorphism

(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

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2-197398035-A-G

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