11-72192181-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016729.3(FOLR1):āc.8A>Gā(p.Gln3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. Q3Q) has been classified as Likely benign.
Frequency
Consequence
NM_016729.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOLR1 | NM_016729.3 | c.8A>G | p.Gln3Arg | missense_variant | 1/4 | ENST00000393676.5 | |
FOLR1 | NM_000802.3 | c.8A>G | p.Gln3Arg | missense_variant | 2/5 | ||
FOLR1 | NM_016724.3 | c.8A>G | p.Gln3Arg | missense_variant | 3/6 | ||
FOLR1 | NM_016725.3 | c.8A>G | p.Gln3Arg | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOLR1 | ENST00000393676.5 | c.8A>G | p.Gln3Arg | missense_variant | 1/4 | 1 | NM_016729.3 | P1 | |
ENST00000378140.3 | n.419+6332T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251366Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74482
ClinVar
Submissions by phenotype
Cerebral folate transport deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 24, 2021 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with FOLR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 3 of the FOLR1 protein (p.Gln3Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at