Variant chr20-45316318-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014276.4(RBPJL):c.1152G>T(p.Pro384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,854 control chromosomes in the GnomAD database, including 34,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2634 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31512 hom. )

Consequence

RBPJL
NM_014276.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.96

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-5.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RBPJL	NM_014276.4 linkuse as main transcript	c.1152G>T	p.Pro384=	synonymous_variant	10/12	ENST00000343694.8	NP_055091.2
RBPJL	XM_011528522.3 linkuse as main transcript	c.1057G>T	p.Gly353Cys	missense_variant	10/12		XP_011526824.1
RBPJL	NM_001281449.2 linkuse as main transcript	c.1152G>T	p.Pro384=	synonymous_variant	10/12		NP_001268378.1
RBPJL	NM_001281448.2 linkuse as main transcript	c.1152G>T	p.Pro384=	synonymous_variant	10/12		NP_001268377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBPJL	ENST00000343694.8 linkuse as main transcript	c.1152G>T	p.Pro384=	synonymous_variant	10/12	1	NM_014276.4	ENSP00000341243	A1	Q9UBG7-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26776

AN:

152124

Hom.:

2633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0188

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.173

AC:

43526

AN:

251052

Hom.:

4331

AF XY:

0.180

AC XY:

24446

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0960

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.0168

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.202

AC:

295859

AN:

1461612

Hom.:

31512

Cov.:

AF XY:

0.202

AC XY:

146935

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.176

AC:

26793

AN:

152242

Hom.:

2634

Cov.:

AF XY:

0.177

AC XY:

13191

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.200

Hom.:

3558

Bravo

AF:

0.165

Asia WGS

AF:

0.0870

AC:

302

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.42

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over