rs35704760
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_003227.4(TFR2):c.1770C>T(p.Asp590=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,611,606 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0038 ( 73 hom. )
Consequence
TFR2
NM_003227.4 splice_region, synonymous
NM_003227.4 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.30
Genes affected
TFR2 (HGNC:11762): (transferrin receptor 2) This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 7-100627489-G-A is Benign according to our data. Variant chr7-100627489-G-A is described in ClinVar as [Benign]. Clinvar id is 21368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00349 (531/152326) while in subpopulation SAS AF= 0.0141 (68/4830). AF 95% confidence interval is 0.0114. There are 11 homozygotes in gnomad4. There are 272 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFR2 | NM_003227.4 | c.1770C>T | p.Asp590= | splice_region_variant, synonymous_variant | 16/18 | ENST00000223051.8 | |
LOC124901709 | XR_007060454.1 | n.434-3667G>A | intron_variant, non_coding_transcript_variant | ||||
TFR2 | NM_001206855.3 | c.1257C>T | p.Asp419= | splice_region_variant, synonymous_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFR2 | ENST00000223051.8 | c.1770C>T | p.Asp590= | splice_region_variant, synonymous_variant | 16/18 | 1 | NM_003227.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00348 AC: 529AN: 152208Hom.: 10 Cov.: 33
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GnomAD3 exomes AF: 0.00641 AC: 1571AN: 245126Hom.: 29 AF XY: 0.00693 AC XY: 919AN XY: 132632
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GnomAD4 exome AF: 0.00381 AC: 5559AN: 1459280Hom.: 73 Cov.: 40 AF XY: 0.00426 AC XY: 3089AN XY: 725722
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GnomAD4 genome ? AF: 0.00349 AC: 531AN: 152326Hom.: 11 Cov.: 33 AF XY: 0.00365 AC XY: 272AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:4Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hemochromatosis type 3 Benign:2Other:1
Benign, 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 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. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Hereditary hemochromatosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | TFR2: BS1, BS2 - |
Computational scores
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Name
Calibrated prediction
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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
DS_AG_spliceai
Position offset: -31
Find out detailed SpliceAI scores and Pangolin per-transcript scores at