Variant 4-26320917-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000348160(RBPJ):c.-298G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,602,824 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 22 hom. )

Consequence

RBPJ
ENST00000348160 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.64

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 4-26320917-G-A is Benign according to our data. Variant chr4-26320917-G-A is described in ClinVar as [Benign]. Clinvar id is 444137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000928 (1346/1450830) while in subpopulation AMR AF= 0.0295 (1267/42904). AF 95% confidence interval is 0.0282. There are 22 homozygotes in gnomad4_exome. There are 559 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 221 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
RBPJ	NM_001374400.1 linkuse as main transcript	c.59+102G>A	intron_variant	NP_001361329.1
RBPJ	NM_005349.4 linkuse as main transcript	c.59+102G>A	intron_variant	NP_005340.2	Q06330-1
RBPJ	NM_001374401.1 linkuse as main transcript	c.-166-41529G>A	intron_variant	NP_001361330.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
RBPJ	ENST00000348160 linkuse as main transcript	c.-298G>A	5_prime_UTR_variant	1/12	1	ENSP00000339699.5	Q06330-6
RBPJ	ENST00000361572.10 linkuse as main transcript	c.59+102G>A	intron_variant		1	ENSP00000354528.6	Q06330-1
RBPJ	ENST00000345843.8 linkuse as main transcript	c.-47+1029G>A	intron_variant		1	ENSP00000305815.6	Q06330-5

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

151876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000928

AC:

1346

AN:

1450830

Hom.:

Cov.:

AF XY:

0.000776

AC XY:

559

AN XY:

720474

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.000817

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

151994

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

106

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000916

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00332

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

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