20-45314036-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_014276.4(RBPJL):c.759T>C(p.Ala253=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,611,092 control chromosomes in the GnomAD database, including 5,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.046 ( 476 hom., cov: 33)

Exomes 𝑓: 0.052 ( 4724 hom. )

Consequence

RBPJL
NM_014276.4 splice_region, synonymous

Scores

Splicing: ADA: 0.001287

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.362

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 20-45314036-T-C is Benign according to our data. Variant chr20-45314036-T-C is described in ClinVar as [Benign]. Clinvar id is 444110.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.362 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RBPJL	NM_014276.4 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12	ENST00000343694.8
RBPJL	NM_001281449.2 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12
RBPJL	NM_001281448.2 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12
RBPJL	XM_011528522.3 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJL	ENST00000343694.8 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12	1	NM_014276.4	A1	Q9UBG7-1
RBPJL	ENST00000372743.5 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12	1		P4	Q9UBG7-2
RBPJL	ENST00000372741.7 linkuse as main transcript	c.759T>C	p.Ala253=	splice_region_variant, synonymous_variant	8/12	1
RBPJL	ENST00000464504.2 linkuse as main transcript	c.3T>C	p.Ter1=	coding_sequence_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

6955

AN:

152190

Hom.:

475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00933

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0853

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0320

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0912

AC:

22898

AN:

251146

Hom.:

2342

AF XY:

0.0905

AC XY:

12279

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00806

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.349

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0355

Gnomad OTH exome

AF:

0.0630

GnomAD4 exome

AF:

0.0520

AC:

75851

AN:

1458784

Hom.:

4724

Cov.:

AF XY:

0.0546

AC XY:

39653

AN XY:

725862

show subpopulations

Gnomad4 AFR exome

AF:

0.00661

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0544

GnomAD4 genome

AF:

0.0456

AC:

6950

AN:

152308

Hom.:

476

Cov.:

AF XY:

0.0507

AC XY:

3774

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00928

Gnomad4 AMR

AF:

0.0856

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0320

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0452

Hom.:

764

Bravo

AF:

0.0498

Asia WGS

AF:

0.193

AC:

668

AN:

3478

EpiCase

AF:

0.0341

EpiControl

AF:

0.0333

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Type 2 diabetes mellitus

Benign:1

Benign, no assertion criteria provided

case-control

Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.010

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