20-45314071-G-A

Position:

chr20-45314071-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000343694.8(RBPJL):c.794G>A(p.Arg265Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000812 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

RBPJL
ENST00000343694.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Variant links:

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]

RBPJL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029480755).

BS2

High AC in GnomAd4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RBPJL	NM_014276.4 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12	ENST00000343694.8	NP_055091.2
RBPJL	NM_001281449.2 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12		NP_001268378.1
RBPJL	NM_001281448.2 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12		NP_001268377.1
RBPJL	XM_011528522.3 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12		XP_011526824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBPJL	ENST00000343694.8 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12	1	NM_014276.4	ENSP00000341243	A1	Q9UBG7-1
RBPJL	ENST00000372743.5 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12	1		ENSP00000361828	P4	Q9UBG7-2
RBPJL	ENST00000372741.7 linkuse as main transcript	c.794G>A	p.Arg265Gln	missense_variant	8/12	1		ENSP00000361826
RBPJL	ENST00000464504.2 linkuse as main transcript	c.38G>A	p.Arg13Gln	missense_variant	1/5	3		ENSP00000483978

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251372

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000355

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000833

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Oct 26, 2021

The c.794G>A (p.R265Q) alteration is located in exon 8 (coding exon 8) of the RBPJL gene. This alteration results from a G to A substitution at nucleotide position 794, causing the arginine (R) at amino acid position 265 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

.;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;L

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.081

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.089

T;T;T

Polyphen

0.057, 0.0010

.;B;B

Vest4

0.15

MVP

0.35

MPC

0.44

ClinPred

0.059

GERP RS

3.3

Varity_R

0.054

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over