rs2303743
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001127671.2(LIFR):c.1899A>G(p.Ile633Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,613,954 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I633T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127671.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIFR | NM_001127671.2 | c.1899A>G | p.Ile633Met | missense_variant | 14/20 | ENST00000453190.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIFR | ENST00000453190.7 | c.1899A>G | p.Ile633Met | missense_variant | 14/20 | 2 | NM_001127671.2 | P1 | |
LIFR | ENST00000263409.8 | c.1899A>G | p.Ile633Met | missense_variant | 14/20 | 1 | P1 | ||
LIFR | ENST00000503088.1 | n.2062A>G | non_coding_transcript_exon_variant | 14/15 | 1 | ||||
LIFR | ENST00000506003.5 | c.*77A>G | 3_prime_UTR_variant, NMD_transcript_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00718 AC: 1093AN: 152210Hom.: 18 Cov.: 32
GnomAD3 exomes AF: 0.00893 AC: 2245AN: 251436Hom.: 31 AF XY: 0.00754 AC XY: 1024AN XY: 135886
GnomAD4 exome AF: 0.00335 AC: 4900AN: 1461626Hom.: 75 Cov.: 31 AF XY: 0.00318 AC XY: 2314AN XY: 727136
GnomAD4 genome AF: 0.00717 AC: 1092AN: 152328Hom.: 18 Cov.: 32 AF XY: 0.00819 AC XY: 610AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 05, 2017 | - - |
Stuve-Wiedemann syndrome Benign:2
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 specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 06, 2015 | - - |
Stüve-Wiedemann syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 08, 2023 | - - |
Connective tissue disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Oct 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at