dbSNP rs1049728: RELA:c.*732C>G (chr11-65653646-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021975.4(RELA):c.*732C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 152,598 control chromosomes in the GnomAD database, including 289 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 0.049 ( 289 hom., cov: 33)

Exomes 𝑓: 0.066 ( 0 hom. )

Consequence

RELA
NM_021975.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.864

Publications

19 publications found

Variant links:

Genes affected

RELA (HGNC:9955): (RELA proto-oncogene, NF-kB subunit) NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RELA Gene-Disease associations (from GenCC):

combined immunodeficiency due to RELA haploinsufficiency
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
mucocutaneous ulceration, chronic
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary pediatric Behçet-like disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RELA links:

ENSG00000306723 (HGNC:):

ENSG00000306723 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELA	NM_021975.4 link	c.*732C>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000406246.8	NP_068810.3	Q04206-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246.8 link	c.*732C>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_021975.4	ENSP00000384273.3		Q04206-1

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7429

AN:

152162

Hom.:

289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0648

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.0660

AC:

AN:

318

Hom.:

Cov.:

AF XY:

0.0470

AC XY:

AN XY:

234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0465

AC:

AN:

172

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0952

AC:

AN:

126

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0488

AC:

7429

AN:

152280

Hom.:

289

Cov.:

AF XY:

0.0528

AC XY:

3931

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0103

AC:

427

AN:

41562

American (AMR)

AF:

0.0311

AC:

476

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0642

AC:

223

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5192

South Asian (SAS)

AF:

0.0425

AC:

205

AN:

4822

European-Finnish (FIN)

AF:

0.147

AC:

1560

AN:

10588

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0648

AC:

4406

AN:

68024

Other (OTH)

AF:

0.0384

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

385

770

1156

1541

1926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0534

Hom.:

Bravo

AF:

0.0368

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over