rs12609547

Variant names:

• chr19-45028751-G-T
• rs12609547
• NM_006509.4:c.887-137G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006509.4(RELB):​c.887-137G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 636,774 control chromosomes in the GnomAD database, including 57,566 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 0.39 (12027 hom., cov: 32)
  • Exomes 𝑓: 0.43 (45539 hom.)
• Consequence: RELB NM_006509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELB	NM_006509.4	c.887-137G>T		intron_variant	Intron 7 of 11	ENST00000221452.13	NP_006500.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELB	ENST00000221452.13	c.887-137G>T		intron_variant	Intron 7 of 11	1	NM_006509.4	ENSP00000221452.7
RELB	ENST00000505236.2	c.878-137G>T		intron_variant	Intron 6 of 10	5		ENSP00000423287.1
RELB	ENST00000700471.1	n.*219-137G>T		intron_variant	Intron 3 of 7			ENSP00000515004.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59589 AN: 151812 Hom.: 12023 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.427 AC: 206821 AN: 484844 Hom.: 45539 AF XY: 0.435 AC XY: 111462 AN XY: 256022

African (AFR) AF: 0.320 AC: 4187 AN: 13066

American (AMR) AF: 0.507 AC: 10937 AN: 21592

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 6388 AN: 14430

East Asian (EAS) AF: 0.489 AC: 15044 AN: 30742

South Asian (SAS) AF: 0.587 AC: 28374 AN: 48310

European-Finnish (FIN) AF: 0.455 AC: 15553 AN: 34212

Middle Eastern (MID) AF: 0.491 AC: 1653 AN: 3364

European-Non Finnish (NFE) AF: 0.388 AC: 113492 AN: 292220

Other (OTH) AF: 0.416 AC: 11193 AN: 26908

GnomAD4 genome AF: 0.392 AC: 59613 AN: 151930 Hom.: 12027 Cov.: 32 AF XY: 0.401 AC XY: 29787 AN XY: 74240

African (AFR) AF: 0.319 AC: 13230 AN: 41448

American (AMR) AF: 0.466 AC: 7090 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3466

East Asian (EAS) AF: 0.486 AC: 2505 AN: 5150

South Asian (SAS) AF: 0.574 AC: 2765 AN: 4820

European-Finnish (FIN) AF: 0.455 AC: 4805 AN: 10568

Middle Eastern (MID) AF: 0.434 AC: 126 AN: 290

European-Non Finnish (NFE) AF: 0.389 AC: 26434 AN: 67952

Other (OTH) AF: 0.373 AC: 786 AN: 2108

Alfa AF: 0.398 Hom.: 5088

Bravo AF: 0.388

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.78
PhyloP100		-0.10
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: rs12609547; hg19: chr19-45532009; COSMIC: COSV55512462; COSMIC: COSV55512462;