chr19-45032778-C-G

Variant names:

• chr19-45032778-C-G
• rs10424046
• NM_006509.4:c.1207+29C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000221452.13(RELB):​c.1207+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,567,922 control chromosomes in the GnomAD database, including 199,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16844 hom., cov: 31)
  • Exomes 𝑓: 0.51 (182841 hom.)
• Consequence: RELB ENST00000221452.13 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-45032778-C-G is Benign according to our data. Variant chr19-45032778-C-G is described in ClinVar as Benign. ClinVar VariationId is 2628126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000221452.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELB	NM_006509.4	MANE Select	c.1207+29C>G		intron	N/A	NP_006500.2
	RELB	NM_001411087.1		c.1198+29C>G		intron	N/A	NP_001398016.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELB	ENST00000221452.13	TSL:1 MANE Select	c.1207+29C>G		intron	N/A	ENSP00000221452.7
	RELB	ENST00000505236.2	TSL:5	c.1198+29C>G		intron	N/A	ENSP00000423287.1
	RELB	ENST00000589972.1	TSL:3	c.40+29C>G		intron	N/A	ENSP00000468460.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70596 AN: 151816 Hom.: 16844 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.479

GnomAD2 exomes AF: 0.482 AC: 94774 AN: 196428 AF XY: 0.484

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.503

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.507 AC: 717397 AN: 1415988 Hom.: 182841 Cov.: 29 AF XY: 0.504 AC XY: 353403 AN XY: 700568

African (AFR) AF: 0.358 AC: 11614 AN: 32450

American (AMR) AF: 0.423 AC: 16550 AN: 39140

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 11298 AN: 25332

East Asian (EAS) AF: 0.508 AC: 19200 AN: 37760

South Asian (SAS) AF: 0.419 AC: 34372 AN: 81950

European-Finnish (FIN) AF: 0.499 AC: 24966 AN: 50028

Middle Eastern (MID) AF: 0.476 AC: 2414 AN: 5070

European-Non Finnish (NFE) AF: 0.524 AC: 568318 AN: 1085596

Other (OTH) AF: 0.489 AC: 28665 AN: 58662

GnomAD4 genome AF: 0.465 AC: 70622 AN: 151934 Hom.: 16844 Cov.: 31 AF XY: 0.463 AC XY: 34338 AN XY: 74232

African (AFR) AF: 0.359 AC: 14893 AN: 41428

American (AMR) AF: 0.450 AC: 6865 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1557 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2611 AN: 5146

South Asian (SAS) AF: 0.430 AC: 2070 AN: 4816

European-Finnish (FIN) AF: 0.499 AC: 5263 AN: 10554

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35715 AN: 67948

Other (OTH) AF: 0.482 AC: 1017 AN: 2108

Alfa AF: 0.411 Hom.: 2042

Bravo AF: 0.457

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.20
PromoterAI		-0.0030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10424046; hg19: chr19-45536036; COSMIC: COSV55511217;