chr19-35282506-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The ENST00000598398(HAMP):c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,219,920 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
ENST00000598398 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HAMP | ENST00000598398 | c.-72C>T | 5_prime_UTR_variant | Exon 2 of 4 | 2 | ENSP00000471894.1 | ||||
HAMP | ENST00000222304.5 | c.-72C>T | upstream_gene_variant | 1 | NM_021175.4 | ENSP00000222304.2 | ||||
HAMP | ENST00000593580.1 | n.-11C>T | upstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes AF: 0.000933 AC: 142AN: 152232Hom.: 2 Cov.: 32
GnomAD4 exome AF: 0.00112 AC: 1200AN: 1067570Hom.: 2 Cov.: 16 AF XY: 0.00124 AC XY: 677AN XY: 548152
GnomAD4 genome AF: 0.000919 AC: 140AN: 152350Hom.: 2 Cov.: 32 AF XY: 0.000966 AC XY: 72AN XY: 74502
ClinVar
Submissions by phenotype
Hemochromatosis type 2B Uncertain:1
The variant was detected heterozygously in a young patient with pronounced HFE hemochromatosis, who is also homozygous for the HFE variant c.845G>A, p.(Cys282Tyr). The HAMP variant c.-72C>T, p.?, has already been described as possibly pathogenic (Biasiotto et al. 2004, HGMD Professional 2022.4). Furthermore, other regulatory mutations have already been described as causative for juvenile hemochromatosis (including Island et al. 2009). It is listed with an allele frequency of 0.11% (35x heterozygous, 1x homozygous) in control databases (dbSNP rs367646034, gnomAD v2.1.1). Heterozygous pathogenic variants in the HAMP gene have been shown to increase the risk of iron overload in HFE c.845G>A heterozygotes and increase iron load in HFE c.845G>A homozygotes (Merryweather-Clarke et al 2003, Jacolot et al 2004; Piperno et al, geneReviews 2020). We evaluate the HAMP variant c.-72C>T, p.?, as a variant of unclear significance (VUS). -
Hereditary hemochromatosis Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at