chr17-66223717-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000042.3(APOH):c.396G>A(p.Pro132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,614,124 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 17 hom. )
Consequence
APOH
NM_000042.3 synonymous
NM_000042.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.08
Genes affected
APOH (HGNC:616): (apolipoprotein H) Apolipoprotein H, also known as beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a required cofactor for anionic phospholipid binding by the antiphospholipid autoantibodies found in sera of many patients with lupus and primary antiphospholipid syndrome (APS). The anti-beta (2) glycoprotein I antibodies from APS patients, mediate inhibition of activated protein C which has anticoagulant properties. Because beta-2-GPI is the main autoantigen in patients with APS, the disruption of this pathway by autoantibodies may be an important mechanism for thrombosis in patients with APS.[provided by RefSeq, Dec 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 17-66223717-C-T is Benign according to our data. Variant chr17-66223717-C-T is described in ClinVar as [Benign]. Clinvar id is 733532.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.08 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00221 (336/152252) while in subpopulation EAS AF= 0.0189 (98/5184). AF 95% confidence interval is 0.0159. There are 2 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOH | NM_000042.3 | c.396G>A | p.Pro132= | synonymous_variant | 4/8 | ENST00000205948.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOH | ENST00000205948.11 | c.396G>A | p.Pro132= | synonymous_variant | 4/8 | 1 | NM_000042.3 | P1 | |
APOH | ENST00000581797.5 | c.216G>A | p.Pro72= | synonymous_variant | 4/6 | 3 | |||
APOH | ENST00000577982.1 | c.396G>A | p.Pro132= | synonymous_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00222 AC: 338AN: 152134Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00179 AC: 451AN: 251474Hom.: 5 AF XY: 0.00162 AC XY: 220AN XY: 135908
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GnomAD4 exome AF: 0.000962 AC: 1406AN: 1461872Hom.: 17 Cov.: 30 AF XY: 0.000923 AC XY: 671AN XY: 727234
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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 | Invitae | Mar 29, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at