rs807209
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The ENST00000470149.5(HFE):āc.645C>Gā(p.Gly215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 1,614,010 control chromosomes in the GnomAD database, including 721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.038 ( 388 hom., cov: 31)
Exomes š: 0.0051 ( 333 hom. )
Consequence
HFE
ENST00000470149.5 synonymous
ENST00000470149.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.226
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 6-26092637-C-G is Benign according to our data. Variant chr6-26092637-C-G is described in ClinVar as [Benign]. Clinvar id is 1292203.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.226 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HFE | NM_000410.4 | c.617-48C>G | intron_variant | ENST00000357618.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HFE | ENST00000357618.10 | c.617-48C>G | intron_variant | 1 | NM_000410.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0381 AC: 5789AN: 152106Hom.: 383 Cov.: 31
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GnomAD3 exomes AF: 0.0111 AC: 2771AN: 250314Hom.: 145 AF XY: 0.00844 AC XY: 1142AN XY: 135378
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GnomAD4 exome AF: 0.00508 AC: 7424AN: 1461786Hom.: 333 Cov.: 33 AF XY: 0.00457 AC XY: 3323AN XY: 727196
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GnomAD4 genome ? AF: 0.0382 AC: 5814AN: 152224Hom.: 388 Cov.: 31 AF XY: 0.0369 AC XY: 2749AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2018 | - - |
Computational 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