4-26334621-C-T

Position:

• chr4-26334621-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_015874.6(RBPJ):​c.20+13573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,944 control chromosomes in the GnomAD database, including 20,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.52 (20755 hom., cov: 31)
• Consequence: RBPJ NM_015874.6 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0460

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 4-26334621-C-T is Benign according to our data. Variant chr4-26334621-C-T is described in ClinVar as [Benign]. Clinvar id is 444124.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBPJ	NM_015874.6	c.20+13573C>T		intron_variant		ENST00000355476.8	NP_056958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBPJ	ENST00000355476.8	c.20+13573C>T		intron_variant		1	NM_015874.6	ENSP00000347659	P4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79186 AN: 151824 Hom.: 20723 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.522 AC: 79269 AN: 151944 Hom.: 20755 Cov.: 31 AF XY: 0.521 AC XY: 38700 AN XY: 74248

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.508

Alfa AF: 0.525 Hom.: 5525

Bravo AF: 0.523

Asia WGS AF: 0.432 AC: 1507 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus Benign:1

Benign, no assertion criteria provided

case-control

Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.0
DANN	Benign	0.72

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: rs13144326; hg19: chr4-26336243;