3-186666148-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000412.5(HRG):āc.117T>Cā(p.Asn39=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000675 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000070 ( 0 hom. )
Consequence
HRG
NM_000412.5 synonymous
NM_000412.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
HRG (HGNC:5181): (histidine rich glycoprotein) This histidine-rich glycoprotein contains two cystatin-like domains and is located in plasma and platelets. The physiological function has not been determined but it is known that the protein binds heme, dyes and divalent metal ions. The encoded protein also has a peptide that displays antimicrobial activity against C. albicans, E. coli, S. aureus, P. aeruginosa, and E. faecalis. It can inhibit rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. Mutations in this gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HRG | NM_000412.5 | c.117T>C | p.Asn39= | synonymous_variant | 1/7 | ENST00000232003.5 | NP_000403.1 | |
HRG-AS1 | XR_924801.3 | n.291-14277A>G | intron_variant, non_coding_transcript_variant | |||||
HRG | XM_005247415.5 | c.117T>C | p.Asn39= | synonymous_variant | 1/7 | XP_005247472.1 | ||
HRG-AS1 | XR_001741059.2 | n.291-14277A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HRG | ENST00000232003.5 | c.117T>C | p.Asn39= | synonymous_variant | 1/7 | 1 | NM_000412.5 | ENSP00000232003 | P1 | |
HRG-AS1 | ENST00000630178.2 | n.238+52319A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251380Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135862
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GnomAD4 exome AF: 0.0000698 AC: 102AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000756 AC XY: 55AN XY: 727242
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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