rs150121265
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_021175.4(HAMP):c.252G>A(p.Thr84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,602,518 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00095 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0014 ( 2 hom. )
Consequence
HAMP
NM_021175.4 synonymous
NM_021175.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.61
Genes affected
HAMP (HGNC:15598): (hepcidin antimicrobial peptide) The product encoded by this gene is involved in the maintenance of iron homeostasis, and it is necessary for the regulation of iron storage in macrophages, and for intestinal iron absorption. The preproprotein is post-translationally cleaved into mature peptides of 20, 22 and 25 amino acids, and these active peptides are rich in cysteines, which form intramolecular bonds that stabilize their beta-sheet structures. These peptides exhibit antimicrobial activity against bacteria and fungi. Mutations in this gene cause hemochromatosis type 2B, also known as juvenile hemochromatosis, a disease caused by severe iron overload that results in cardiomyopathy, cirrhosis, and endocrine failure. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 19-35285039-G-A is Benign according to our data. Variant chr19-35285039-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 219770.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-5.61 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HAMP | NM_021175.4 | c.252G>A | p.Thr84= | synonymous_variant | 3/3 | ENST00000222304.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HAMP | ENST00000222304.5 | c.252G>A | p.Thr84= | synonymous_variant | 3/3 | 1 | NM_021175.4 | P1 | |
HAMP | ENST00000598398.5 | c.252G>A | p.Thr84= | synonymous_variant | 4/4 | 2 | P1 | ||
HAMP | ENST00000593580.1 | n.2523G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000946 AC: 144AN: 152158Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000795 AC: 200AN: 251472Hom.: 0 AF XY: 0.000853 AC XY: 116AN XY: 135912
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GnomAD4 exome AF: 0.00143 AC: 2073AN: 1450240Hom.: 2 Cov.: 28 AF XY: 0.00136 AC XY: 981AN XY: 722402
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GnomAD4 genome ? AF: 0.000946 AC: 144AN: 152278Hom.: 0 Cov.: 31 AF XY: 0.000873 AC XY: 65AN XY: 74464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hemochromatosis type 2B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hereditary hemochromatosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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