Variant 4-26319881-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001379409.1(RBPJ):c.7G>C(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000751 in 1,597,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

RBPJ
NM_001379409.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.601

Variant links:

Genes affected

RBPJ (HGNC:5724): (recombination signal binding protein for immunoglobulin kappa J region) The protein encoded by this gene is a transcriptional regulator important in the Notch signaling pathway. The encoded protein acts as a repressor when not bound to Notch proteins and an activator when bound to Notch proteins. It is thought to function by recruiting chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins to Notch signaling pathway genes. Several transcript variants encoding different isoforms have been found for this gene, and several pseudogenes of this gene exist on chromosome 9. [provided by RefSeq, Oct 2013]

RBPJ links:

RBPJ (HGNC:):

RBPJ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RBPJ. . Gene score misZ 3.5749 (greater than the threshold 3.09). Trascript score misZ 3.6233 (greater than threshold 3.09). GenCC has associacion of gene with Adams-Oliver syndrome 3, Adams-Oliver syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.04999429).

BP6

Variant 4-26319881-G-C is Benign according to our data. Variant chr4-26319881-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654701.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
RBPJ	NM_001379409.1 linkuse as main transcript	c.7G>C	p.Gly3Arg	missense_variant	1/10	NP_001366338.1
RBPJ	NM_005349.4 linkuse as main transcript	c.-65G>C		5_prime_UTR_variant	1/12	NP_005340.2	Q06330-1
RBPJ	NM_001379406.1 linkuse as main transcript	c.-174G>C		5_prime_UTR_variant	1/12	NP_001366335.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
RBPJ	ENST00000345843 linkuse as main transcript	c.-54G>C	5_prime_UTR_variant	1/11	1	ENSP00000305815.6	Q06330-5
RBPJ	ENST00000342295 linkuse as main transcript	c.-65G>C	5_prime_UTR_variant	1/12	5	ENSP00000345206.1	Q06330-1
RBPJ	ENST00000512671.6 linkuse as main transcript	c.-58+111G>C	intron_variant		2	ENSP00000423644.2	Q06330-1D6R946

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000988

AC:

AN:

242998

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

132236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000692

AC:

100

AN:

1445194

Hom.:

Cov.:

AF XY:

0.0000764

AC XY:

AN XY:

719710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000855

Gnomad4 OTH exome

AF:

0.0000836

GnomAD4 genome

AF:

0.000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

RBPJ: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.6

DANN

Uncertain

0.98

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.47

M_CAP

Benign

0.0088

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.53

REVEL

Benign

0.024

Sift

Benign

0.079

Sift4G

Benign

0.16

Polyphen

0.52

Vest4

0.11

MutPred

0.21

Gain of methylation at G3 (P = 0.0157);

MVP

0.13

ClinPred

0.058

GERP RS

-0.94

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