20-45312291-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014276.4(RBPJL):c.515G>A(p.Arg172Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,074 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
RBPJL
NM_014276.4 missense
NM_014276.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 4.20
Genes affected
RBPJL (HGNC:13761): (recombination signal binding protein for immunoglobulin kappa J region like) This gene encodes a member of the suppressor of hairless protein family. A similar protein in mouse is a transcription factor that binds to DNA sequences almost identical to that bound by the Notch receptor signaling pathway transcription factor recombining binding protein J. The mouse protein has been shown to activate transcription in concert with Epstein-Barr virus nuclear antigen-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2203936).
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBPJL | NM_014276.4 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | ENST00000343694.8 | |
RBPJL | NM_001281449.2 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | ||
RBPJL | NM_001281448.2 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | ||
RBPJL | XM_011528522.3 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBPJL | ENST00000343694.8 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | 1 | NM_014276.4 | A1 | |
RBPJL | ENST00000372743.5 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | 1 | P4 | ||
RBPJL | ENST00000372741.7 | c.515G>A | p.Arg172Gln | missense_variant | 6/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248658Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134688
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727210
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74386
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The c.515G>A (p.R172Q) alteration is located in exon 6 (coding exon 6) of the RBPJL gene. This alteration results from a G to A substitution at nucleotide position 515, causing the arginine (R) at amino acid position 172 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.98, 0.96
.;D;D
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at