rs11933540

Variant names:

• chr4-26118379-T-C
• rs11933540
• XM_047415656.1:c.-50+12601T>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+12601T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,058 control chromosomes in the GnomAD database, including 11,305 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 0.36 (11305 hom., cov: 32)
• Consequence: RBPJ XM_047415656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 29 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBPJ	XM_047415656.1	c.-50+12601T>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: 0.356 AC: 54124 AN: 151940 Hom.: 11270 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.356 AC: 54204 AN: 152058 Hom.: 11305 Cov.: 32 AF XY: 0.347 AC XY: 25819 AN XY: 74350

African (AFR) AF: 0.562 AC: 23294 AN: 41438

American (AMR) AF: 0.273 AC: 4178 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 949 AN: 3466

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.129 AC: 621 AN: 4828

European-Finnish (FIN) AF: 0.299 AC: 3165 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20900 AN: 67958

Other (OTH) AF: 0.341 AC: 720 AN: 2110

Alfa AF: 0.325 Hom.: 14582

Bravo AF: 0.366

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs11933540; hg19: chr4-26120001;