10-113589182-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004132.5(HABP2):c.*813C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000797 in 856,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 1 hom. )
Consequence
HABP2
NM_004132.5 3_prime_UTR
NM_004132.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.180
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]
NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS2
High AC in GnomAd4 at 142 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HABP2 | NM_004132.5 | c.*813C>T | 3_prime_UTR_variant | 13/13 | ENST00000351270.4 | ||
NRAP | NM_198060.4 | c.5089-103G>A | intron_variant | ENST00000359988.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HABP2 | ENST00000351270.4 | c.*813C>T | 3_prime_UTR_variant | 13/13 | 1 | NM_004132.5 | P1 | ||
NRAP | ENST00000359988.4 | c.5089-103G>A | intron_variant | 1 | NM_198060.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000934 AC: 142AN: 152106Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000768 AC: 541AN: 704774Hom.: 1 Cov.: 9 AF XY: 0.000728 AC XY: 266AN XY: 365532
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GnomAD4 genome AF: 0.000933 AC: 142AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00126 AC XY: 94AN XY: 74430
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Factor VII Marburg I Variant Thrombophilia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational 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