chr20-45309643-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014276.4(RBPJL):c.208C>T(p.Arg70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70Q) has been classified as Benign.
Frequency
Consequence
NM_014276.4 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 |
---|---|---|---|---|---|---|---|
RBPJL | NM_014276.4 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | ENST00000343694.8 | |
RBPJL | NM_001281449.2 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | ||
RBPJL | NM_001281448.2 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | ||
RBPJL | XM_011528522.3 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBPJL | ENST00000343694.8 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | 1 | NM_014276.4 | A1 | |
RBPJL | ENST00000372743.5 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | 1 | P4 | ||
RBPJL | ENST00000372741.7 | c.208C>T | p.Arg70Trp | missense_variant | 3/12 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250562Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135408
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461144Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 726870
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.208C>T (p.R70W) alteration is located in exon 3 (coding exon 3) of the RBPJL gene. This alteration results from a C to T substitution at nucleotide position 208, causing the arginine (R) at amino acid position 70 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at