rs147321650
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_030665.4(RAI1):āc.3532C>Gā(p.Leu1178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,528 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 ā ). Synonymous variant affecting the same amino acid position (i.e. L1178L) has been classified as Likely benign.
Frequency
Consequence
NM_030665.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.3532C>G | p.Leu1178Val | missense_variant | 3/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.3532C>G | p.Leu1178Val | missense_variant | 3/6 | 1 | NM_030665.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459312Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 726028
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74362
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1178 of the RAI1 protein (p.Leu1178Val). This variant is present in population databases (rs147321650, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RAI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 521264). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAI1 protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at