rs4803789

Variant names:

• chr19-45020111-T-G
• rs4803789
• NM_006509.4:c.505-1942T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

RELB Gene-Disease associations (from GenCC):

• immunodeficiency 53

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006509.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELB	NM_006509.4	MANE Select	c.505-1942T>G		intron	N/A	NP_006500.2
	RELB	NM_001411087.1		c.496-1942T>G		intron	N/A	NP_001398016.1	D6R992

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELB	ENST00000221452.13	TSL:1 MANE Select	c.505-1942T>G		intron	N/A	ENSP00000221452.7	Q01201
	RELB	ENST00000505236.2	TSL:5	c.496-1942T>G		intron	N/A	ENSP00000423287.1	D6R992
	RELB	ENST00000700471.1		n.343-5218T>G		intron	N/A	ENSP00000515004.1	A0A8V8TQY2

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

African (AFR) AF: 0.690 AC: 28600 AN: 41468

American (AMR) AF: 0.613 AC: 9315 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2275 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4138 AN: 5184

South Asian (SAS) AF: 0.564 AC: 2722 AN: 4830

European-Finnish (FIN) AF: 0.629 AC: 6640 AN: 10556

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43491 AN: 67958

Other (OTH) AF: 0.673 AC: 1422 AN: 2114

Alfa AF: 0.637 Hom.: 18109

Bravo AF: 0.660

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.2
DANN	Benign	0.30
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4803789; hg19: chr19-45523369;