Variant 4-26320500-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000345843.8(RBPJ):c.-47+612G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 471,404 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

RBPJ
ENST00000345843.8 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.979

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:

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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=-0.68).

BP6

Variant 4-26320500-G-T is Benign according to our data. Variant chr4-26320500-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1179953.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00819 (1247/152268) while in subpopulation AFR AF= 0.0283 (1177/41538). AF 95% confidence interval is 0.027. There are 12 homozygotes in gnomad4. There are 600 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
RBPJ	NM_001374400.1 linkuse as main transcript	c.-57-200G>T	intron_variant	NP_001361329.1
RBPJ	NM_001374401.1 linkuse as main transcript	c.-166-41946G>T	intron_variant	NP_001361330.1
RBPJ	NM_001379406.1 linkuse as main transcript	c.-167+612G>T	intron_variant	NP_001366335.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
RBPJ	ENST00000345843.8 linkuse as main transcript	c.-47+612G>T	intron_variant	1	ENSP00000305815	Q06330-5
RBPJ	ENST00000342295.6 linkuse as main transcript	c.-57-200G>T	intron_variant	5	ENSP00000345206	Q06330-1
RBPJ	ENST00000506956.5 linkuse as main transcript	c.-167+730G>T	intron_variant	4	ENSP00000425750

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1244

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00860

GnomAD4 exome

AF:

0.00104

AC:

332

AN:

319136

Hom.:

AF XY:

0.000853

AC XY:

142

AN XY:

166466

show subpopulations

Gnomad4 AFR exome

AF:

0.0318

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000152

Gnomad4 OTH exome

AF:

0.00216

GnomAD4 genome

AF:

0.00819

AC:

1247

AN:

152268

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

600

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0283

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00955

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

GeneDx

Aug 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.61

DANN

Benign

0.77

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