20-45316318-G-T

Variant names:

• chr20-45316318-G-T
• rs2741500
• NM_014276.4:c.1152G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014276.4(RBPJL):​c.1152G>T​(p.Pro384Pro) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBPJL	NM_014276.4	c.1152G>T	p.Pro384Pro	synonymous_variant	Exon 10 of 12	ENST00000343694.8	NP_055091.2
RBPJL	XM_011528522.3	c.1057G>T	p.Gly353Cys	missense_variant	Exon 10 of 12		XP_011526824.1
RBPJL	NM_001281449.2	c.1152G>T	p.Pro384Pro	synonymous_variant	Exon 10 of 12		NP_001268378.1
RBPJL	NM_001281448.2	c.1152G>T	p.Pro384Pro	synonymous_variant	Exon 10 of 12		NP_001268377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBPJL	ENST00000343694.8	c.1152G>T	p.Pro384Pro	synonymous_variant	Exon 10 of 12	1	NM_014276.4	ENSP00000341243.3

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

GnomAD2 exomes AF: 0.173 AC: 43526 AN: 251052 AF XY: 0.180

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 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

African (AFR) AF: 0.105 AC: 3524 AN: 33476

American (AMR) AF: 0.101 AC: 4505 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4814 AN: 26136

East Asian (EAS) AF: 0.0126 AC: 502 AN: 39694

South Asian (SAS) AF: 0.169 AC: 14597 AN: 86248

European-Finnish (FIN) AF: 0.241 AC: 12865 AN: 53402

Middle Eastern (MID) AF: 0.253 AC: 1455 AN: 5744

European-Non Finnish (NFE) AF: 0.218 AC: 242013 AN: 1111814

Other (OTH) AF: 0.192 AC: 11584 AN: 60382

GnomAD4 genome AF: 0.176 AC: 26793 AN: 152242 Hom.: 2634 Cov.: 33 AF XY: 0.177 AC XY: 13191 AN XY: 74428

African (AFR) AF: 0.114 AC: 4742 AN: 41548

American (AMR) AF: 0.157 AC: 2396 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5188

South Asian (SAS) AF: 0.150 AC: 726 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2602 AN: 10606

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14802 AN: 67998

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.198 Hom.: 5101

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
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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