chr1-63774491-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_005012.4(ROR1):c.74G>A(p.Arg25His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,145,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005012.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROR1 | NM_005012.4 | c.74G>A | p.Arg25His | missense_variant | 1/9 | ENST00000371079.6 | |
ROR1 | NM_001083592.2 | c.74G>A | p.Arg25His | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROR1 | ENST00000371079.6 | c.74G>A | p.Arg25His | missense_variant | 1/9 | 1 | NM_005012.4 | P1 | |
ROR1 | ENST00000371080.5 | c.74G>A | p.Arg25His | missense_variant | 1/7 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000671 AC: 1AN: 149058Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000100 AC: 1AN: 996530Hom.: 0 Cov.: 30 AF XY: 0.00000211 AC XY: 1AN XY: 474774
GnomAD4 genome ? AF: 0.00000671 AC: 1AN: 149058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72636
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2021 | The c.74G>A (p.R25H) alteration is located in exon 1 (coding exon 1) of the ROR1 gene. This alteration results from a G to A substitution at nucleotide position 74, causing the arginine (R) at amino acid position 25 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 25 of the ROR1 protein (p.Arg25His). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ROR1-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at