rs4803789

chr19-45020111-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006509.4(RELB):c.505-1942T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,984 control chromosomes in the GnomAD database, including 32,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32677 hom., cov: 32)
• Consequence: RELB NM_006509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

Genes affected

RELB (HGNC:9956): (RELB proto-oncogene, NF-kB subunit) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and protein kinase binding activity. Involved in lymphocyte differentiation and negative regulation of interferon-beta production. Located in cytosol and nucleoplasm. Part of chromatin; nucleus; and transcription repressor complex. Colocalizes with centrosome. Implicated in breast cancer and immunodeficiency 53. Biomarker of breast cancer and transitional cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELB	NM_006509.4	c.505-1942T>G		intron_variant		ENST00000221452.13
RELB	NM_001411087.1	c.496-1942T>G		intron_variant
RELB	XM_005259128.3	c.505-1942T>G		intron_variant
RELB	XM_047439189.1	c.94-1942T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELB	ENST00000221452.13	c.505-1942T>G		intron_variant		1	NM_006509.4	P2
RELB	ENST00000505236.2	c.496-1942T>G		intron_variant		5		A2
RELB	ENST00000700471.1	c.343-5218T>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99367 AN: 151866 Hom.: 32641 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.654 AC: 99462 AN: 151984 Hom.: 32677 Cov.: 32 AF XY: 0.655 AC XY: 48664 AN XY: 74294

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.673

Alfa AF: 0.637 Hom.: 16523

Bravo AF: 0.660

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	3.2
Dann	Benign	0.30

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: rs4803789; hg19: chr19-45523369;