NM_001374401.1:c.-166-71513C>T

Variant names:

• chr4-26290933-C-T
• rs2871198
• NM_001374401.1:c.-166-71513C>T

Variant summary

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

The NM_001374401.1(RBPJ):​c.-166-71513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 150,378 control chromosomes in the GnomAD database, including 31,216 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 0.62 (31216 hom., cov: 32)
• Consequence: RBPJ NM_001374401.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 6 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

ENSG00000302045 (HGNC:58749):

LOC105374542 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBPJ	NM_001374401.1	c.-166-71513C>T		intron_variant	Intron 1 of 11		NP_001361330.1
RBPJ	XM_047415656.1	c.78-95420C>T		intron_variant	Intron 2 of 11		XP_047271612.1
LOC105374542	XR_925508.3	n.70-2484G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBPJ	ENST00000512351.5	c.-166-71513C>T		intron_variant	Intron 1 of 4	4		ENSP00000424789.1
RBPJ	ENST00000681403.1	n.86-71513C>T		intron_variant	Intron 1 of 9
RBPJ	ENST00000681799.1	n.-167+27219C>T		intron_variant	Intron 2 of 12			ENSP00000504876.1
ENSG00000302045	ENST00000783594.1	n.70-2484G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 93842 AN: 150258 Hom.: 31173 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.625 AC: 93938 AN: 150378 Hom.: 31216 Cov.: 32 AF XY: 0.619 AC XY: 45445 AN XY: 73372

African (AFR) AF: 0.712 AC: 29159 AN: 40940

American (AMR) AF: 0.629 AC: 9514 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2058 AN: 3450

East Asian (EAS) AF: 0.394 AC: 1971 AN: 5006

South Asian (SAS) AF: 0.452 AC: 2148 AN: 4756

European-Finnish (FIN) AF: 0.605 AC: 6289 AN: 10392

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 40854 AN: 67424

Other (OTH) AF: 0.606 AC: 1266 AN: 2090

Alfa AF: 0.612 Hom.: 45801

Asia WGS AF: 0.441 AC: 1529 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.012
DANN	Benign	0.39
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs2871198; hg19: chr4-26292555;