rs1045537
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000410.4(HFE):c.*2294G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 456,408 control chromosomes in the GnomAD database, including 2,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.11 ( 1031 hom., cov: 31)
Exomes 𝑓: 0.086 ( 1357 hom. )
Consequence
HFE
NM_000410.4 3_prime_UTR
NM_000410.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.566
Genes affected
HFE (HGNC:4886): (homeostatic iron regulator) The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. [provided by RefSeq, May 2022]
H2BC4 (HGNC:4757): (H2B clustered histone 4) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. The protein has antibacterial and antifungal antimicrobial activity. The main transcript variant of this gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. This transcript variant lacks a polyA tail but instead contains a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Apr 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HFE | NM_000410.4 | c.*2294G>C | 3_prime_UTR_variant | 6/6 | ENST00000357618.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HFE | ENST00000357618.10 | c.*2294G>C | 3_prime_UTR_variant | 6/6 | 1 | NM_000410.4 | P3 | ||
H2BC4 | ENST00000707188.1 | c.*10-5486C>G | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.109 AC: 16618AN: 152120Hom.: 1029 Cov.: 31
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GnomAD3 exomes AF: 0.0818 AC: 11192AN: 136790Hom.: 577 AF XY: 0.0808 AC XY: 6004AN XY: 74348
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GnomAD4 exome AF: 0.0857 AC: 26069AN: 304170Hom.: 1357 Cov.: 0 AF XY: 0.0815 AC XY: 14115AN XY: 173222
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GnomAD4 genome ? AF: 0.109 AC: 16635AN: 152238Hom.: 1031 Cov.: 31 AF XY: 0.105 AC XY: 7846AN XY: 74438
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ClinVar
Not reported inComputational scores
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Name
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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