rs201007090
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000128.4(F11):c.1556G>A(p.Trp519*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000128.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.1556G>A | p.Trp519* | stop_gained | Exon 13 of 15 | 1 | NM_000128.4 | ENSP00000384957.2 | ||
F11-AS1 | ENST00000505103.5 | n.1006-224C>T | intron_variant | Intron 3 of 3 | 1 | |||||
F11 | ENST00000264691.4 | c.175+677G>A | intron_variant | Intron 1 of 2 | 3 | ENSP00000264691.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251434Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461582Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727090
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Pathogenic:3
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not provided Pathogenic:2
PP5, PM1_supporting, PM2_moderate, PM3_very_strong, PS4_moderate, PVS1 -
This sequence change creates a premature translational stop signal (p.Trp519*) in the F11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F11 are known to be pathogenic (PMID: 23929304). This variant is present in population databases (rs201007090, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with factor XI deficiency (PMID: 11122101, 20015217). This variant is also known as p.501*. ClinVar contains an entry for this variant (Variation ID: 188887). For these reasons, this variant has been classified as Pathogenic. -
Abnormal bleeding Pathogenic:1
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Plasma factor XI deficiency Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at