rs7080536
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2
The NM_004132.5(HABP2):c.1601G>A(p.Gly534Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,420 control chromosomes in the GnomAD database, including 1,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 54 hom., cov: 32)
Exomes 𝑓: 0.035 ( 1069 hom. )
Consequence
HABP2
NM_004132.5 missense
NM_004132.5 missense
Scores
9
5
2
Clinical Significance
Conservation
PhyloP100: 9.29
Genes affected
HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Eigen, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009163111).
BP6
?
Variant 10-113588287-G-A is Benign according to our data. Variant chr10-113588287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 5974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-113588287-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.023 (3503/152236) while in subpopulation NFE AF= 0.0375 (2549/67994). AF 95% confidence interval is 0.0363. There are 54 homozygotes in gnomad4. There are 1671 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3503 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HABP2 | NM_004132.5 | c.1601G>A | p.Gly534Glu | missense_variant | 13/13 | ENST00000351270.4 | |
HABP2 | NM_001177660.3 | c.1523G>A | p.Gly508Glu | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HABP2 | ENST00000351270.4 | c.1601G>A | p.Gly534Glu | missense_variant | 13/13 | 1 | NM_004132.5 | P1 | |
HABP2 | ENST00000542051.5 | c.1523G>A | p.Gly508Glu | missense_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0230 AC: 3501AN: 152118Hom.: 54 Cov.: 32
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GnomAD3 exomes AF: 0.0223 AC: 5608AN: 251244Hom.: 89 AF XY: 0.0231 AC XY: 3132AN XY: 135788
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GnomAD4 exome AF: 0.0350 AC: 51163AN: 1461184Hom.: 1069 Cov.: 30 AF XY: 0.0342 AC XY: 24836AN XY: 726928
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GnomAD4 genome ? AF: 0.0230 AC: 3503AN: 152236Hom.: 54 Cov.: 32 AF XY: 0.0224 AC XY: 1671AN XY: 74438
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170
ALSPAC
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199
ESP6500AA
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ExAC
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
FACTOR VII-ACTIVATING PROTEASE MARBURG I POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Nov 19, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2021 | This variant is associated with the following publications: (PMID: 21789270, 26691890, 22421107, 27873212, 22906531, 26222560, 28089742, 17145954, 26745718, 19105210, 26832773, 12578864, 28222214, 28418605, 28884020, 28402931, 30070759, 32162184, 33025555, 33488516) - |
Factor VII Marburg I Variant Thrombophilia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Venous thromboembolism, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 19, 2015 | - - |
THYROID CANCER, NONMEDULLARY, 5, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 19, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MPC
0.058
ClinPred
T
GERP RS
Varity_R
gMVP
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