4-26350741-T-G

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+29693T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,108 control chromosomes in the GnomAD database, including 37,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.70 (37820 hom., cov: 32)
• Consequence: RBPJ NM_015874.6 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.376

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=-0.93).
• BP6: Variant 4-26350741-T-G is Benign according to our data. Variant chr4-26350741-T-G is described in ClinVar as [Benign]. Clinvar id is 444136.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJ	NM_015874.6	c.20+29693T>G		intron_variant		ENST00000355476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000355476.8	c.20+29693T>G		intron_variant		1	NM_015874.6	P4

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106681 AN: 151990 Hom.: 37760 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.702 AC: 106800 AN: 152108 Hom.: 37820 Cov.: 32 AF XY: 0.704 AC XY: 52350 AN XY: 74362

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.688

Alfa AF: 0.652 Hom.: 5323

Bravo AF: 0.711

Asia WGS AF: 0.730 AC: 2539 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	-0.93
Cadd	Benign	6.2
Dann	Benign	0.80

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: rs6853254; hg19: chr4-26352363;