rs1054082920

Variant names:

• chr19-45001617-C-G
• rs1054082920
• NM_006509.4:c.38C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-45001617-C-G
• chr19-45001617-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006509.4(RELB):​c.38C>G​(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,367,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: RELB NM_006509.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14324975).

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.38C>G	p.Pro13Arg	missense	Exon 1 of 12	NP_006500.2
	RELB	NM_001411087.1		c.38C>G	p.Pro13Arg	missense	Exon 1 of 11	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.38C>G	p.Pro13Arg	missense	Exon 1 of 12	ENSP00000221452.7	Q01201
	RELB	ENST00000505236.2	TSL:5	c.38C>G	p.Pro13Arg	missense	Exon 1 of 11	ENSP00000423287.1	D6R992
	RELB	ENST00000509480.5	TSL:3	n.38C>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000427348.1	D6RIV7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367562 Hom.: 0 Cov.: 30 AF XY: 0.00000297 AC XY: 2 AN XY: 674392

African (AFR) AF: 0.00 AC: 0 AN: 29718

American (AMR) AF: 0.00 AC: 0 AN: 34540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24738

East Asian (EAS) AF: 0.00 AC: 0 AN: 33648

South Asian (SAS) AF: 0.00 AC: 0 AN: 77584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4396

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1072270

Other (OTH) AF: 0.00 AC: 0 AN: 57162

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.70
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.031
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.21	B
Vest4		0.21
MutPred		0.25		Gain of MoRF binding (P = 0.0056)
MVP		0.46
MPC		0.61
ClinPred		0.17	T
GERP RS		1.4
PromoterAI		-0.050	Neutral
Varity_R		0.10
gMVP		0.31
Mutation Taster		=93/7	polymorphism

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: rs1054082920; hg19: chr19-45504875;