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1-149923950-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005850.5(SF3B4):c.978C>A(p.Pro326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,589,084 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

SF3B4
NM_005850.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0760
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-149923950-G-T is Benign according to our data. Variant chr1-149923950-G-T is described in ClinVar as [Benign]. Clinvar id is 292475.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.076 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00145 (221/152210) while in subpopulation EAS AF= 0.0393 (203/5160). AF 95% confidence interval is 0.0349. There are 6 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 224 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SF3B4NM_005850.5 linkuse as main transcriptc.978C>A p.Pro326= synonymous_variant 5/6 ENST00000271628.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SF3B4ENST00000271628.9 linkuse as main transcriptc.978C>A p.Pro326= synonymous_variant 5/61 NM_005850.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00147
AC:
224
AN:
152092
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0398
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00341
AC:
731
AN:
214246
Hom.:
13
AF XY:
0.00299
AC XY:
355
AN XY:
118708
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000755
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0477
Gnomad SAS exome
AF:
0.000411
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000200
Gnomad OTH exome
AF:
0.000792
GnomAD4 exome
AF:
0.00120
AC:
1724
AN:
1436874
Hom.:
29
Cov.:
32
AF XY:
0.00111
AC XY:
793
AN XY:
715230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000536
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0381
Gnomad4 SAS exome
AF:
0.000481
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000905
Gnomad4 OTH exome
AF:
0.00372
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
221
AN:
152210
Hom.:
6
Cov.:
32
AF XY:
0.00172
AC XY:
128
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0393
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.000555
Hom.:
0
Bravo
AF:
0.00169
Asia WGS
AF:
0.0140
AC:
51
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 15, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
5.9
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs58383987; hg19: chr1-149895842; API