rs8178610
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000313.4(PROS1):c.77-145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 964,236 control chromosomes in the GnomAD database, including 86,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.35 ( 10729 hom., cov: 30)
Exomes 𝑓: 0.42 ( 75688 hom. )
Consequence
PROS1
NM_000313.4 intron
NM_000313.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.146
Genes affected
PROS1 (HGNC:9456): (protein S) This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. It is found in plasma in both a free, functionally active form and also in an inactive form complexed with C4b-binding protein. Mutations in this gene result in autosomal dominant hereditary thrombophilia. An inactive pseudogene of this locus is located at an adjacent region on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 3-93927552-C-T is Benign according to our data. Variant chr3-93927552-C-T is described in ClinVar as [Benign]. Clinvar id is 1264572.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROS1 | NM_000313.4 | c.77-145G>A | intron_variant | ENST00000394236.9 | |||
PROS1 | NM_001314077.2 | c.173-145G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROS1 | ENST00000394236.9 | c.77-145G>A | intron_variant | 1 | NM_000313.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.355 AC: 53824AN: 151642Hom.: 10723 Cov.: 30
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GnomAD4 exome AF: 0.422 AC: 342726AN: 812476Hom.: 75688 AF XY: 0.427 AC XY: 175917AN XY: 412398
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GnomAD4 genome ? AF: 0.355 AC: 53834AN: 151760Hom.: 10729 Cov.: 30 AF XY: 0.360 AC XY: 26679AN XY: 74132
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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 | GeneDx | Jul 09, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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