Variant chr2-197392351-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012433.4(SF3B1):c.3867C>T(p.Asn1289=) 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

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=-0.47).

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. Variant chr2-197392351-G-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 951 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SF3B1	NM_012433.4 linkuse as main transcript	c.3867C>T	p.Asn1289=	synonymous_variant	25/25	ENST00000335508.11
SF3B1	XM_047443838.1 linkuse as main transcript	c.3429C>T	p.Asn1143=	synonymous_variant	22/22
SF3B1	XM_047443839.1 linkuse as main transcript	c.3429C>T	p.Asn1143=	synonymous_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3B1	ENST00000335508.11 linkuse as main transcript	c.3867C>T	p.Asn1289=	synonymous_variant	25/25	1	NM_012433.4	P1	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

GnomAD3 exomes

AF:

0.00599

AC:

1498

AN:

250280

Hom.:

AF XY:

0.00593

AC XY:

802

AN XY:

135286

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 SAS exome

AF:

0.000428

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

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.000990

Gnomad4 ASJ exome

AF:

0.00686

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.000332

Gnomad4 FIN exome

AF:

0.00804

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00691

GnomAD4 genome

AF:

0.00625

AC:

951

AN:

152208

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

447

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00983

Gnomad4 NFE

AF:

0.00991

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00804

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

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

-0.47

CADD

Benign

6.4

DANN

Benign

0.68

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