rs115070660

Variant names:

Variant summary

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

The NM_005850.5(SF3B4):c.682T>C(p.Leu228Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,611,792 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 30 hom., cov: 32)

Exomes 𝑓: 0.024 ( 506 hom. )

Consequence

SF3B4
NM_005850.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.08

Variant links:

Genes affected

SF3B4 (HGNC:10771): (splicing factor 3b subunit 4) This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq, Jul 2008]

SF3B4 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=-0.94).

BP6

Variant 1-149926400-A-G is Benign according to our data. Variant chr1-149926400-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 130291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2480/152230) while in subpopulation NFE AF= 0.0269 (1828/67998). AF 95% confidence interval is 0.0259. There are 30 homozygotes in gnomad4. There are 1188 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2480 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B4	NM_005850.5 link	c.682T>C	p.Leu228Leu	synonymous_variant	Exon 3 of 6	ENST00000271628.9	NP_005841.1	Q15427B3KUJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B4	ENST00000271628.9 link	c.682T>C	p.Leu228Leu	synonymous_variant	Exon 3 of 6	1	NM_005850.5	ENSP00000271628.8		Q15427
SF3B4	ENST00000457312.1 link	c.553T>C	p.Leu185Leu	synonymous_variant	Exon 3 of 3	5		ENSP00000391114.1		Q5SZ64

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2481

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00451

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0176

AC:

4398

AN:

250452

Hom.:

AF XY:

0.0180

AC XY:

2436

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.00419

Gnomad AMR exome

AF:

0.00988

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.0151

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0188

GnomAD4 exome

AF:

0.0238

AC:

34719

AN:

1459562

Hom.:

506

Cov.:

AF XY:

0.0234

AC XY:

16956

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.00389

Gnomad4 AMR exome

AF:

0.00952

Gnomad4 ASJ exome

AF:

0.00376

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0163

AC:

2480

AN:

152230

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1188

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00450

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0210

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0287

EpiControl

AF:

0.0266

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 22, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.24

DANN

Benign

0.52

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