20-45316318-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.96

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]

ACMG classification

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	UniProt
RBPJL	NM_014276.4	c.1152G>T	p.Pro384=	synonymous_variant	10/12	ENST00000343694.8
RBPJL	XM_011528522.3	c.1057G>T	p.Gly353Cys	missense_variant	10/12
RBPJL	NM_001281449.2	c.1152G>T	p.Pro384=	synonymous_variant	10/12
RBPJL	NM_001281448.2	c.1152G>T	p.Pro384=	synonymous_variant	10/12

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26776 AN: 152124 Hom.: 2633 Cov.: 33

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

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.: 34 AF XY: 0.202 AC XY: 146935 AN XY: 727080

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.: 33 AF XY: 0.177 AC XY: 13191 AN XY: 74428

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

Other links and lift over

dbSNP: rs2741500; hg19: chr20-43944958; COSMIC: COSV59213924;