2-197392351-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012433.4(SF3B1):c.3867C>T(p.Asn1289Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,534,372 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 63 hom. )

Consequence

SF3B1
NM_012433.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.888

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-197392351-G-A is Benign according to our data. Variant chr2-197392351-G-A is described in ClinVar as [Benign]. Clinvar id is 790342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.888 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00625 (951/152208) while in subpopulation NFE AF = 0.00991 (674/68012). AF 95% confidence interval is 0.00929. There are 6 homozygotes in GnomAd4. There are 447 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 951 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B1	NM_012433.4 link	c.3867C>T	p.Asn1289Asn	synonymous_variant	Exon 25 of 25	ENST00000335508.11	NP_036565.2	O75533-1B4DGZ4
SF3B1	XM_047443838.1 link	c.3429C>T	p.Asn1143Asn	synonymous_variant	Exon 22 of 22		XP_047299794.1
SF3B1	XM_047443839.1 link	c.3429C>T	p.Asn1143Asn	synonymous_variant	Exon 22 of 22		XP_047299795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B1	ENST00000335508.11 link	c.3867C>T	p.Asn1289Asn	synonymous_variant	Exon 25 of 25	1	NM_012433.4	ENSP00000335321.6		O75533-1

Frequencies

GnomAD3 genomes

AF:

0.00625

AC:

951

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00983

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00991

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00599

AC:

1498

AN:

250280

AF XY:

0.00593

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000876

Gnomad ASJ exome

AF:

0.00805

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00973

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00890

AC:

12301

AN:

1382164

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

5925

AN XY:

692322

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

31756

American (AMR)

AF:

0.000990

AC:

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.00686

AC:

176

AN:

25670

East Asian (EAS)

AF:

0.000102

AC:

AN:

39340

South Asian (SAS)

AF:

0.000332

AC:

AN:

84408

European-Finnish (FIN)

AF:

0.00804

AC:

429

AN:

53372

Middle Eastern (MID)

AF:

0.000355

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.0108

AC:

11183

AN:

1039850

Other (OTH)

AF:

0.00691

AC:

399

AN:

57714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

492

984

1477

1969

2461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00625

AC:

951

AN:

152208

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

447

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41532

American (AMR)

AF:

0.00131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00983

AC:

104

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00991

AC:

674

AN:

68012

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00943

Hom.:

Bravo

AF:

0.00597

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.00861

EpiControl

AF:

0.00784

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.4

(source)

DANN

Benign

0.68

PhyloP100

0.89

Mutation Taster

=100/0

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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2-197392351-G-A

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