rs3817939
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000133.4(F9):c.88+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 899,344 control chromosomes in the GnomAD database, including 1,463 homozygotes. There are 10,267 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.038 ( 180 hom., 1411 hem., cov: 23)
Exomes 𝑓: 0.037 ( 1283 hom. 8856 hem. )
Consequence
F9
NM_000133.4 intron
NM_000133.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.997
Genes affected
F9 (HGNC:3551): (coagulation factor IX) This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant X-139530927-A-G is Benign according to our data. Variant chrX-139530927-A-G is described in ClinVar as [Benign]. Clinvar id is 2775452.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F9 | NM_000133.4 | c.88+75A>G | intron_variant | ENST00000218099.7 | |||
F9 | NM_001313913.2 | c.88+75A>G | intron_variant | ||||
F9 | XM_005262397.5 | c.88+75A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F9 | ENST00000218099.7 | c.88+75A>G | intron_variant | 1 | NM_000133.4 | P1 | |||
F9 | ENST00000394090.2 | c.88+75A>G | intron_variant | 1 | |||||
F9 | ENST00000479617.2 | n.95+75A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0382 AC: 4276AN: 111896Hom.: 178 Cov.: 23 AF XY: 0.0414 AC XY: 1412AN XY: 34082
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GnomAD4 exome AF: 0.0369 AC: 29074AN: 787394Hom.: 1283 AF XY: 0.0415 AC XY: 8856AN XY: 213578
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GnomAD4 genome ? AF: 0.0382 AC: 4274AN: 111950Hom.: 180 Cov.: 23 AF XY: 0.0413 AC XY: 1411AN XY: 34146
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary factor IX deficiency disease Benign:1
Benign, reviewed by expert panel | curation | ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen | Feb 09, 2024 | The c.88+75A>G variant is reported at an MAF of 0.1727 (1595/9236 alleles) in the Latino population in gnomAD v3 with 580 hemizygotes and 103 homozygotes, meeting BA1 criteria of MAF > 0.0000556. The variant is listed as a polymorphism in the EAHAD database. SpliceAI predicts no impact on splicing, which meets the BP4 criteria. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: BA1, BP4. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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