chr19-45001684-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006509.4(RELB):c.105A>C(p.Leu35Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,511,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

RELB
NM_006509.4 missense, splice_region

Scores

Splicing: ADA: 0.02334

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.843

Publications

0 publications found

Variant links:

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)

RELB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.13542193).

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.105A>C	p.Leu35Phe	missense splice_region	Exon 1 of 12	NP_006500.2
	RELB	NM_001411087.1		c.105A>C	p.Leu35Phe	missense splice_region	Exon 1 of 11	NP_001398016.1	D6R992

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RELB	ENST00000221452.13	TSL:1 MANE Select	c.105A>C	p.Leu35Phe	missense splice_region	Exon 1 of 12	ENSP00000221452.7	Q01201
RELB	ENST00000505236.2	TSL:5	c.105A>C	p.Leu35Phe	missense splice_region	Exon 1 of 11	ENSP00000423287.1	D6R992
RELB	ENST00000509480.5	TSL:3	n.105A>C		splice_region non_coding_transcript_exon	Exon 1 of 5	ENSP00000427348.1	D6RIV7

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000860

AC:

AN:

116322

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000459

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1359428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30046

American (AMR)

AF:

0.0000295

AC:

AN:

33908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24600

East Asian (EAS)

AF:

0.00

AC:

AN:

33866

South Asian (SAS)

AF:

0.00

AC:

AN:

77318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064916

Other (OTH)

AF:

0.00

AC:

AN:

56798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151780

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.000131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67860

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.84

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.0

REVEL

Benign

0.093

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.036

Polyphen

0.91

Vest4

0.18

MutPred

0.13

Loss of catalytic residue at L35 (P = 0.0853)

MVP

0.26

MPC

0.83

ClinPred

0.22

GERP RS

0.92

PromoterAI

0.015

Neutral

(source)

Varity_R

0.12

gMVP

0.19

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.023

dbscSNV1_RF

Benign

0.48

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over