chr4-26120053-T-C

Variant names:

• chr4-26120053-T-C
• rs2048506
• XM_047415656.1:c.-50+14275T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047415656.1(RBPJ):​c.-50+14275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,060 control chromosomes in the GnomAD database, including 18,701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18701 hom., cov: 32)
• Consequence: RBPJ XM_047415656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBPJ	XM_047415656.1	c.-50+14275T>C		intron_variant	Intron 1 of 11		XP_047271612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72378 AN: 151942 Hom.: 18666 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.476 AC: 72450 AN: 152060 Hom.: 18701 Cov.: 32 AF XY: 0.466 AC XY: 34610 AN XY: 74328

African (AFR) AF: 0.633 AC: 26239 AN: 41476

American (AMR) AF: 0.388 AC: 5928 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5176

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4504 AN: 10540

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31318 AN: 67970

Other (OTH) AF: 0.476 AC: 1007 AN: 2114

Alfa AF: 0.461 Hom.: 2927

Bravo AF: 0.481

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.51
PhyloP100		-0.089

Splicing

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

Other links and lift over

dbSNP: rs2048506; hg19: chr4-26121675;