rs115070660

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Nager acrofacial dysostosis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
SF3B4-related acrofacial dysostosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
acrofacial dysostosis Rodriguez type
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SF3B4 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=-0.94).

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.0176

AC:

4398

AN:

250452

AF XY:

0.0180

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 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

African (AFR)

AF:

0.00389

AC:

130

AN:

33440

American (AMR)

AF:

0.00952

AC:

425

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00376

AC:

AN:

26070

East Asian (EAS)

AF:

0.000101

AC:

AN:

39628

South Asian (SAS)

AF:

0.0130

AC:

1124

AN:

86196

European-Finnish (FIN)

AF:

0.0145

AC:

774

AN:

53400

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0278

AC:

30899

AN:

1110142

Other (OTH)

AF:

0.0194

AC:

1171

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1743

3486

5229

6972

8715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0163

AC:

2480

AN:

152230

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1188

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00450

AC:

187

AN:

41550

American (AMR)

AF:

0.0131

AC:

200

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0106

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0139

AC:

147

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0269

AC:

1828

AN:

67998

Other (OTH)

AF:

0.0204

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

127

255

382

510

637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00799

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

Aug 22, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.24

(source)

DANN

Benign

0.52

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs115070660

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