9-74630294-T-G
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2
The NM_006914.4(RORB):c.20T>G(p.Val7Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006914.4 missense
Scores
Clinical Significance
Conservation
Publications
- epilepsy, idiopathic generalized, susceptibility to, 15Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- complex neurodevelopmental disorderInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- epilepsyInheritance: AD Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461036Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726852 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2008088). This variant has not been reported in the literature in individuals affected with RORB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 7 of the RORB protein (p.Val7Gly). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at