1-155900379-ATCTTC-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006912.6(RIT1):c.*4_*8delGAAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,602,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006912.6 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RIT1 | NM_006912.6 | c.*4_*8delGAAGA | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000368323.8 | NP_008843.1 | ||
RIT1 | NM_001256821.2 | c.*4_*8delGAAGA | 3_prime_UTR_variant | Exon 6 of 6 | NP_001243750.1 | |||
RIT1 | NM_001256820.2 | c.*4_*8delGAAGA | 3_prime_UTR_variant | Exon 5 of 5 | NP_001243749.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251136Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135754
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1450004Hom.: 0 AF XY: 0.00000969 AC XY: 7AN XY: 722092
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: RIT1 c.*4_*8delGAAGA is located in the untranslated mRNA region downstream of the termination codon. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251136 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.*4_*8delGAAGA in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -
RIT1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at