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17-66228102-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_000042.3(APOH):c.159G>T(p.Pro53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,614,188 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0056 ( 38 hom. )

Consequence

APOH
NM_000042.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.28
Variant links:
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 -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-66228102-C-A is Benign according to our data. Variant chr17-66228102-C-A is described in ClinVar as [Benign]. Clinvar id is 784362.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.28 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOHNM_000042.3 linkuse as main transcriptc.159G>T p.Pro53= synonymous_variant 2/8 ENST00000205948.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOHENST00000205948.11 linkuse as main transcriptc.159G>T p.Pro53= synonymous_variant 2/81 NM_000042.3 P1
APOHENST00000577982.1 linkuse as main transcriptc.159G>T p.Pro53= synonymous_variant 3/65
APOHENST00000581797.5 linkuse as main transcriptc.-22G>T 5_prime_UTR_variant 2/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00411
AC:
626
AN:
152200
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00152
Gnomad AMI
AF:
0.0461
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00682
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00336
AC:
846
AN:
251476
Hom.:
1
AF XY:
0.00339
AC XY:
461
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00143
Gnomad NFE exome
AF:
0.00622
Gnomad OTH exome
AF:
0.00440
GnomAD4 exome
AF:
0.00560
AC:
8184
AN:
1461870
Hom.:
38
Cov.:
31
AF XY:
0.00539
AC XY:
3917
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000926
Gnomad4 AMR exome
AF:
0.00121
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000336
Gnomad4 FIN exome
AF:
0.00157
Gnomad4 NFE exome
AF:
0.00690
Gnomad4 OTH exome
AF:
0.00498
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00411
AC:
626
AN:
152318
Hom.:
1
Cov.:
32
AF XY:
0.00356
AC XY:
265
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00152
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00682
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00420
Hom.:
1
Bravo
AF:
0.00393
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00671
EpiControl
AF:
0.00587

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 submitterclinical testingInvitaeJul 10, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
0.031
Dann
Benign
0.62
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs55772214; hg19: chr17-64224220; API