4-26320420-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000345843.8(RBPJ):c.-47+532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 342,192 control chromosomes in the GnomAD database, including 7,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (4971 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2366 hom.)
• Consequence: RBPJ ENST00000345843.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.902

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-26320420-G-A is Benign according to our data. Variant chr4-26320420-G-A is described in ClinVar as [Benign]. Clinvar id is 1283151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJ	NM_001374400.1	c.-57-280G>A		intron_variant
RBPJ	NM_001374401.1	c.-166-42026G>A		intron_variant
RBPJ	NM_001379406.1	c.-167+532G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000345843.8	c.-47+532G>A		intron_variant		1
RBPJ	ENST00000342295.6	c.-57-280G>A		intron_variant		5
RBPJ	ENST00000506956.5	c.-167+650G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30539 AN: 151934 Hom.: 4956 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.127 AC: 24165 AN: 190140 Hom.: 2366 AF XY: 0.122 AC XY: 11979 AN XY: 97806

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.0571

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.0727

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.201 AC: 30596 AN: 152052 Hom.: 4971 Cov.: 32 AF XY: 0.200 AC XY: 14861 AN XY: 74326

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0603

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.179

Alfa AF: 0.195 Hom.: 684

Bravo AF: 0.216

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.4
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs7657866; hg19: chr4-26322042;