4-26386337-AT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_015874.6(RBPJ):c.21-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24380 hom., cov: 0)
  • Exomes 𝑓: 0.58 (180522 hom.)
• Consequence: RBPJ NM_015874.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.300

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 -16 ACMG points.

• BP6: Variant 4-26386337-AT-A is Benign according to our data. Variant chr4-26386337-AT-A is described in ClinVar as [Benign]. Clinvar id is 1164945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJ	NM_015874.6	c.21-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000355476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000355476.8	c.21-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015874.6	P4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 85587 AN: 149536 Hom.: 24341 Cov.: 0

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.569

GnomAD3 exomes AF: 0.628 AC: 119655 AN: 190628 Hom.: 31063 AF XY: 0.627 AC XY: 64295 AN XY: 102516

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.597

Gnomad SAS exome AF: 0.616

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.615

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.580 AC: 724816 AN: 1249684 Hom.: 180522 Cov.: 0 AF XY: 0.581 AC XY: 361813 AN XY: 622508

Gnomad4 AFR exome AF: 0.554

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.573 AC: 85680 AN: 149646 Hom.: 24380 Cov.: 0 AF XY: 0.574 AC XY: 41906 AN XY: 73014

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.567

Bravo AF: 0.571

Asia WGS AF: 0.559 AC: 1933 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56122711; hg19: chr4-26387959;