rs1800758
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000410.4(HFE):c.892+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,608 control chromosomes in the GnomAD database, including 13,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.13 ( 1368 hom., cov: 31)
Exomes 𝑓: 0.13 ( 12605 hom. )
Consequence
HFE
NM_000410.4 intron
NM_000410.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.259
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 6-26093008-G-A is Benign according to our data. Variant chr6-26093008-G-A is described in ClinVar as [Benign]. Clinvar id is 14.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26093008-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HFE | NM_000410.4 | c.892+48G>A | intron_variant | ENST00000357618.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HFE | ENST00000357618.10 | c.892+48G>A | intron_variant | 1 | NM_000410.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.131 AC: 19932AN: 152040Hom.: 1367 Cov.: 31
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GnomAD3 exomes AF: 0.132 AC: 33142AN: 250950Hom.: 2594 AF XY: 0.137 AC XY: 18621AN XY: 135692
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GnomAD4 exome AF: 0.126 AC: 183977AN: 1461450Hom.: 12605 Cov.: 35 AF XY: 0.129 AC XY: 93694AN XY: 727038
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GnomAD4 genome ? AF: 0.131 AC: 19938AN: 152158Hom.: 1368 Cov.: 31 AF XY: 0.131 AC XY: 9759AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2018 | - - |
HFE INTRONIC POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Nov 01, 1999 | - - |
Computational scores
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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