Variant 2-197398035-A-G 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.3216T>C(p.Ala1072=) 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. In-silico tool predicts a benign outcome for this variant. 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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

BS2

High AC in GnomAd4 at 696 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SF3B1	NM_012433.4 linkuse as main transcript	c.3216T>C	p.Ala1072=	synonymous_variant	22/25	ENST00000335508.11
SF3B1	XM_047443838.1 linkuse as main transcript	c.2778T>C	p.Ala926=	synonymous_variant	19/22
SF3B1	XM_047443839.1 linkuse as main transcript	c.2778T>C	p.Ala926=	synonymous_variant	19/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3B1	ENST00000335508.11 linkuse as main transcript	c.3216T>C	p.Ala1072=	synonymous_variant	22/25	1	NM_012433.4	P1	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

GnomAD3 exomes

AF:

0.00469

AC:

1179

AN:

251384

Hom.:

AF XY:

0.00497

AC XY:

675

AN XY:

135870

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 SAS exome

AF:

0.00487

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

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00525

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.00799

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152312

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00784

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00495

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

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	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SF3B1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

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