chrX-154836305-T-C
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000132.4(F8):c.*1292A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.99 ( 38426 hom., 32204 hem., cov: 22)
Exomes 𝑓: 1.0 ( 1 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
F8
NM_000132.4 3_prime_UTR
NM_000132.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.16
Genes affected
F8 (HGNC:3546): (coagulation factor VIII) This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F8 | NM_000132.4 | c.*1292A>G | 3_prime_UTR_variant | 26/26 | ENST00000360256.9 | ||
F8 | NM_019863.3 | c.*1292A>G | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F8 | ENST00000360256.9 | c.*1292A>G | 3_prime_UTR_variant | 26/26 | 1 | NM_000132.4 | P1 | ||
F8 | ENST00000330287.10 | c.*1292A>G | 3_prime_UTR_variant | 5/5 | 1 | ||||
F8 | ENST00000644698.1 | c.*1292A>G | 3_prime_UTR_variant | 6/6 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 109478AN: 110136Hom.: 38430 Cov.: 22 AF XY: 0.995 AC XY: 32141AN XY: 32314 FAILED QC
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GnomAD4 exome AF: 1.00 AC: 3AN: 3Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 1AN XY: 1
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GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.994 AC: 109532AN: 110191Hom.: 38426 Cov.: 22 AF XY: 0.995 AC XY: 32204AN XY: 32379
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Data not reliable, filtered out with message: InbreedingCoeff
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at