17-17794528-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_030665.4(RAI1):c.1580G>A(p.Arg527His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R527C) has been classified as Uncertain significance.
Frequency
Consequence
NM_030665.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.1580G>A | p.Arg527His | missense_variant | 3/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.1580G>A | p.Arg527His | missense_variant | 3/6 | 1 | NM_030665.4 | P1 | |
RAI1 | ENST00000395774.1 | c.1580G>A | p.Arg527His | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248518Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135006
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460412Hom.: 0 Cov.: 93 AF XY: 0.0000165 AC XY: 12AN XY: 726528
GnomAD4 genome AF: 0.000131 AC: 20AN: 152362Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74516
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 06, 2014 | - - |
RAI1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 01, 2023 | The RAI1 c.1580G>A variant is predicted to result in the amino acid substitution p.Arg527His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.041% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-17697842-G-A). Although we suspect this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at