chr16-72060449-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1
The NM_005143.5(HP):c.780G>A(p.Glu260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,614,158 control chromosomes in the GnomAD database, including 1,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.031 ( 131 hom., cov: 31)
Exomes 𝑓: 0.046 ( 1823 hom. )
Consequence
HP
NM_005143.5 synonymous
NM_005143.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.620
Genes affected
HP (HGNC:5141): (haptoglobin) This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 16-72060449-G-A is Benign according to our data. Variant chr16-72060449-G-A is described in ClinVar as [Benign]. Clinvar id is 3060365.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.62 with no splicing effect.
BA1
?
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HP | NM_005143.5 | c.780G>A | p.Glu260= | synonymous_variant | 7/7 | ENST00000355906.10 | |
HP | NM_001126102.3 | c.603G>A | p.Glu201= | synonymous_variant | 5/5 | ||
HP | NM_001318138.2 | c.603G>A | p.Glu201= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HP | ENST00000355906.10 | c.780G>A | p.Glu260= | synonymous_variant | 7/7 | 1 | NM_005143.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0315 AC: 4789AN: 152170Hom.: 131 Cov.: 31
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GnomAD3 exomes AF: 0.0307 AC: 7665AN: 249438Hom.: 179 AF XY: 0.0312 AC XY: 4224AN XY: 135326
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GnomAD4 exome AF: 0.0463 AC: 67668AN: 1461870Hom.: 1823 Cov.: 31 AF XY: 0.0453 AC XY: 32923AN XY: 727236
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GnomAD4 genome ? AF: 0.0314 AC: 4789AN: 152288Hom.: 131 Cov.: 31 AF XY: 0.0322 AC XY: 2396AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HP-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at