4-26320827-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000348160.9(RBPJ):c.-388G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,561,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: RBPJ ENST00000348160.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 4-26320827-G-C is Benign according to our data. Variant chr4-26320827-G-C is described in ClinVar as [Benign]. Clinvar id is 1622500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBPJ	NM_001374400.1	c.59+12G>C		intron_variant
RBPJ	NM_001374401.1	c.-166-41619G>C		intron_variant
RBPJ	NM_001379406.1	c.-167+939G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJ	ENST00000348160.9	c.-388G>C		5_prime_UTR_variant	1/12	1		A1
RBPJ	ENST00000345843.8	c.-47+939G>C		intron_variant		1
RBPJ	ENST00000361572.10	c.59+12G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152228 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000263 AC: 44 AN: 167068 Hom.: 0 AF XY: 0.000203 AC XY: 18 AN XY: 88540

Gnomad AFR exome AF: 0.00386

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 146 AN: 1408800 Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 73 AN XY: 695480

Gnomad4 AFR exome AF: 0.00308

Gnomad4 AMR exome AF: 0.000195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000175

Gnomad4 OTH exome AF: 0.000257

GnomAD4 genome AF: 0.00106 AC: 162 AN: 152346 Hom.: 2 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74488

Gnomad4 AFR AF: 0.00358

Gnomad4 AMR AF: 0.000522

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.000738 Hom.: 0

Bravo AF: 0.00118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 15, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	17
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200338350; hg19: chr4-26322449;