chr2-197398499-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_012433.4(SF3B1):c.3096A>G(p.Gln1032=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00059 ( 0 hom. )
Consequence
SF3B1
NM_012433.4 synonymous
NM_012433.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.20
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 2-197398499-T-C is Benign according to our data. Variant chr2-197398499-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035547.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00046 (70/152300) while in subpopulation AMR AF= 0.000849 (13/15308). AF 95% confidence interval is 0.000547. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 70 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B1 | NM_012433.4 | c.3096A>G | p.Gln1032= | synonymous_variant | 21/25 | ENST00000335508.11 | |
SF3B1 | XM_047443838.1 | c.2658A>G | p.Gln886= | synonymous_variant | 18/22 | ||
SF3B1 | XM_047443839.1 | c.2658A>G | p.Gln886= | synonymous_variant | 18/22 | ||
SF3B1 | XM_047443840.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B1 | ENST00000335508.11 | c.3096A>G | p.Gln1032= | synonymous_variant | 21/25 | 1 | NM_012433.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000374 AC: 94AN: 251128Hom.: 0 AF XY: 0.000354 AC XY: 48AN XY: 135718
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GnomAD4 exome AF: 0.000590 AC: 862AN: 1461552Hom.: 0 Cov.: 31 AF XY: 0.000569 AC XY: 414AN XY: 727090
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SF3B1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at