4-26383713-G-A

Variant summary

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

The NM_015874.6(RBPJ):c.21-2640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,890 control chromosomes in the GnomAD database, including 24,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.56 (24150 hom., cov: 32)
• Consequence: RBPJ NM_015874.6 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.106

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=-0.7).
• BP6: Variant 4-26383713-G-A is Benign according to our data. Variant chr4-26383713-G-A is described in ClinVar as [Benign]. Clinvar id is 444128.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJ	NM_015874.6	c.21-2640G>A		intron_variant		ENST00000355476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000355476.8	c.21-2640G>A		intron_variant		1	NM_015874.6	P4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85260 AN: 151772 Hom.: 24112 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.562 AC: 85354 AN: 151890 Hom.: 24150 Cov.: 32 AF XY: 0.563 AC XY: 41828 AN XY: 74234

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.561

Alfa AF: 0.563 Hom.: 6743

Bravo AF: 0.565

Asia WGS AF: 0.561 AC: 1951 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.4
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7655165; hg19: chr4-26385335;