chr12-50986965-T-C
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_000617.3(SLC11A2):c.*1360A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,287,168 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 5 hom. )
Consequence
SLC11A2
NM_000617.3 3_prime_UTR
NM_000617.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.27
Genes affected
SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000919 (14/152340) while in subpopulation SAS AF= 0.00249 (12/4828). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC11A2 | NM_000617.3 | c.*1360A>G | 3_prime_UTR_variant | 16/16 | ENST00000262052.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC11A2 | ENST00000262052.9 | c.*1360A>G | 3_prime_UTR_variant | 16/16 | 1 | NM_000617.3 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000445 AC: 58AN: 130272Hom.: 1 AF XY: 0.000534 AC XY: 38AN XY: 71112
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GnomAD4 exome AF: 0.000211 AC: 240AN: 1134828Hom.: 5 Cov.: 35 AF XY: 0.000300 AC XY: 167AN XY: 556682
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74500
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Microcytic anemia with liver iron overload Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
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