rs139633601
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_016729.3(FOLR1):c.508G>A(p.Ala170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,614,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A170S) has been classified as Uncertain significance.
Frequency
Consequence
NM_016729.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOLR1 | NM_016729.3 | c.508G>A | p.Ala170Thr | missense_variant | 4/4 | ENST00000393676.5 | |
FOLR1 | NM_000802.3 | c.508G>A | p.Ala170Thr | missense_variant | 5/5 | ||
FOLR1 | NM_016724.3 | c.508G>A | p.Ala170Thr | missense_variant | 6/6 | ||
FOLR1 | NM_016725.3 | c.508G>A | p.Ala170Thr | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOLR1 | ENST00000393676.5 | c.508G>A | p.Ala170Thr | missense_variant | 4/4 | 1 | NM_016729.3 | P1 | |
ENST00000378140.3 | n.419+2602C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00154 AC: 235AN: 152202Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000370 AC: 93AN: 251464Hom.: 0 AF XY: 0.000316 AC XY: 43AN XY: 135900
GnomAD4 exome AF: 0.000157 AC: 229AN: 1461892Hom.: 1 Cov.: 33 AF XY: 0.000135 AC XY: 98AN XY: 727248
GnomAD4 genome ? AF: 0.00154 AC: 235AN: 152320Hom.: 1 Cov.: 33 AF XY: 0.00148 AC XY: 110AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 08, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 29, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2020 | - - |
Cerebral folate transport deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 03, 2019 | - - |
FOLR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 15, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at