rs13008848
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_014585.6(SLC40A1):c.-98G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,601,060 control chromosomes in the GnomAD database, including 35,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2425 hom., cov: 33)
Exomes 𝑓: 0.21 ( 32864 hom. )
Consequence
SLC40A1
NM_014585.6 5_prime_UTR
NM_014585.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.62
Genes affected
SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
Variant 2-189580558-C-G is Benign according to our data. Variant chr2-189580558-C-G is described in ClinVar as [Benign]. Clinvar id is 260421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC40A1 | NM_014585.6 | c.-98G>C | 5_prime_UTR_variant | 1/8 | ENST00000261024.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC40A1 | ENST00000261024.7 | c.-98G>C | 5_prime_UTR_variant | 1/8 | 1 | NM_014585.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.157 AC: 23809AN: 152086Hom.: 2424 Cov.: 33
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GnomAD3 exomes AF: 0.166 AC: 38940AN: 235258Hom.: 3808 AF XY: 0.172 AC XY: 21978AN XY: 127772
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GnomAD4 exome AF: 0.206 AC: 298890AN: 1448854Hom.: 32864 Cov.: 34 AF XY: 0.206 AC XY: 148279AN XY: 720772
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GnomAD4 genome ? AF: 0.156 AC: 23809AN: 152206Hom.: 2425 Cov.: 33 AF XY: 0.154 AC XY: 11485AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hemochromatosis type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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