rs1439195599
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_000128.4(F11):c.1136-7_1136-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000128.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11 | NM_000128.4 | c.1136-7_1136-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.1136-7_1136-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000128.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461880Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727240
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 05, 2018 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | This sequence change falls in intron 10 of the F11 gene. It does not directly change the encoded amino acid sequence of the F11 protein. It affects a nucleotide within the consensus splice site. For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 15946525, 27067486). ClinVar contains an entry for this variant (Variation ID: 555987). This variant has been observed in individuals with Factor XI deficiency (PMID: 15946525, 27067486). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.006%). - |
Plasma factor XI deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at