20-45309178-T-C

Variant summary

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

The NM_014276.4(RBPJL):c.132-389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 151,866 control chromosomes in the GnomAD database, including 448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.051 (448 hom., cov: 31)
• Consequence: RBPJL NM_014276.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0640

Genes affected

RBPJL (HGNC:13761): (recombination signal binding protein for immunoglobulin kappa J region like) This gene encodes a member of the suppressor of hairless protein family. A similar protein in mouse is a transcription factor that binds to DNA sequences almost identical to that bound by the Notch receptor signaling pathway transcription factor recombining binding protein J. The mouse protein has been shown to activate transcription in concert with Epstein-Barr virus nuclear antigen-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-45309178-T-C is Benign according to our data. Variant chr20-45309178-T-C is described in ClinVar as [Benign]. Clinvar id is 444114.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJL	NM_014276.4	c.132-389T>C		intron_variant		ENST00000343694.8
RBPJL	NM_001281448.2	c.132-389T>C		intron_variant
RBPJL	NM_001281449.2	c.132-389T>C		intron_variant
RBPJL	XM_011528522.3	c.132-389T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJL	ENST00000343694.8	c.132-389T>C		intron_variant		1	NM_014276.4	A1
RBPJL	ENST00000372741.7	c.132-389T>C		intron_variant		1
RBPJL	ENST00000372743.5	c.132-389T>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7731 AN: 151752 Hom.: 447 Cov.: 31

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0512

Gnomad OTH AF: 0.0493

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

GnomAD4 genome AF: 0.0509 AC: 7724 AN: 151866 Hom.: 448 Cov.: 31 AF XY: 0.0520 AC XY: 3863 AN XY: 74238

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0502 Hom.: 43

Bravo AF: 0.0511

Asia WGS AF: 0.197 AC: 684 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	-0.91
Cadd	Benign	4.3
Dann	Benign	0.49

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: rs2076027; hg19: chr20-43937818;