chr2-197392351-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_012433.4(SF3B1):c.3867C>T(p.Asn1289=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,534,372 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0062 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0089 ( 63 hom. )
Consequence
SF3B1
NM_012433.4 synonymous
NM_012433.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.888
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=-0.47).
BP6
?
Variant 2-197392351-G-A is Benign according to our data. Variant chr2-197392351-G-A is described in ClinVar as [Benign]. Clinvar id is 790342.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-197392351-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.888 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00625 (951/152208) while in subpopulation NFE AF= 0.00991 (674/68012). AF 95% confidence interval is 0.00929. There are 6 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 951 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B1 | NM_012433.4 | c.3867C>T | p.Asn1289= | synonymous_variant | 25/25 | ENST00000335508.11 | |
SF3B1 | XM_047443838.1 | c.3429C>T | p.Asn1143= | synonymous_variant | 22/22 | ||
SF3B1 | XM_047443839.1 | c.3429C>T | p.Asn1143= | synonymous_variant | 22/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B1 | ENST00000335508.11 | c.3867C>T | p.Asn1289= | synonymous_variant | 25/25 | 1 | NM_012433.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00625 AC: 951AN: 152090Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00599 AC: 1498AN: 250280Hom.: 7 AF XY: 0.00593 AC XY: 802AN XY: 135286
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GnomAD4 exome AF: 0.00890 AC: 12301AN: 1382164Hom.: 63 Cov.: 24 AF XY: 0.00856 AC XY: 5925AN XY: 692322
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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 submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at