ENST00000361572.10:c.10_24delACGGAGGGCTCGCCC

Variant names:

• chr4-26320764-ACACGGAGGGCTCGCC-A
• ENST00000361572.10:c.10_24delACGGAGGGCTCGCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The ENST00000361572.10(RBPJ):​c.10_24delACGGAGGGCTCGCCC​(p.Thr4_Pro8del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBPJ ENST00000361572.10 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000361572.10.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361572.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBPJ	NM_001374400.1		c.10_24delACGGAGGGCTCGCCC	p.Thr4_Pro8del	conservative_inframe_deletion	Exon 2 of 12	NP_001361329.1	Q06330-1
	RBPJ	NM_005349.4		c.10_24delACGGAGGGCTCGCCC	p.Thr4_Pro8del	conservative_inframe_deletion	Exon 2 of 12	NP_005340.2
	RBPJ	NM_001379408.1		c.10_24delACGGAGGGCTCGCCC	p.Thr4_Pro8del	conservative_inframe_deletion	Exon 2 of 11	NP_001366337.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBPJ	ENST00000361572.10	TSL:1	c.10_24delACGGAGGGCTCGCCC	p.Thr4_Pro8del	conservative_inframe_deletion	Exon 1 of 11	ENSP00000354528.6	Q06330-1
	RBPJ	ENST00000345843.8	TSL:1	c.-47+878_-47+892delACGGAGGGCTCGCCC		intron	N/A	ENSP00000305815.6	Q06330-5
	RBPJ	ENST00000342295.6	TSL:5	c.10_24delACGGAGGGCTCGCCC	p.Thr4_Pro8del	conservative_inframe_deletion	Exon 2 of 12	ENSP00000345206.1	Q06330-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-26322386;