dbSNP rs11227247: RELA:c.*205T>G (chr11-65655382-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000525693.5(RELA):c.*205T>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 0.169 in 577,886 control chromosomes in the GnomAD database, including 11,383 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 0.20 ( 3905 hom., cov: 32)

Exomes 𝑓: 0.16 ( 7478 hom. )

Consequence

RELA
ENST00000525693.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

24 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:

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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELA	NM_021975.4 link	c.1033+306T>G		intron_variant	Intron 10 of 10	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.1033+306T>G		intron_variant	Intron 10 of 10	1	NM_021975.4	ENSP00000384273.3		Q04206-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30314

AN:

152000

Hom.:

3900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.0933

Gnomad FIN

AF:

0.0901

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.192

GnomAD4 exome

AF:

0.158

AC:

67443

AN:

425768

Hom.:

7478

Cov.:

AF XY:

0.152

AC XY:

34014

AN XY:

223084

show subpopulations

African (AFR)

AF:

0.308

AC:

3698

AN:

12024

American (AMR)

AF:

0.366

AC:

5875

AN:

16030

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

1583

AN:

13318

East Asian (EAS)

AF:

0.435

AC:

13014

AN:

29940

South Asian (SAS)

AF:

0.0843

AC:

3407

AN:

40434

European-Finnish (FIN)

AF:

0.102

AC:

2921

AN:

28744

Middle Eastern (MID)

AF:

0.125

AC:

237

AN:

1892

European-Non Finnish (NFE)

AF:

0.126

AC:

32496

AN:

258436

Other (OTH)

AF:

0.169

AC:

4212

AN:

24950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2553

5105

7658

10210

12763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30345

AN:

152118

Hom.:

3905

Cov.:

AF XY:

0.199

AC XY:

14803

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.313

AC:

12990

AN:

41452

American (AMR)

AF:

0.310

AC:

4738

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3472

East Asian (EAS)

AF:

0.375

AC:

1936

AN:

5164

South Asian (SAS)

AF:

0.0936

AC:

451

AN:

4820

European-Finnish (FIN)

AF:

0.0901

AC:

956

AN:

10614

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8318

AN:

67998

Other (OTH)

AF:

0.190

AC:

401

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1194

2388

3583

4777

5971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.146

Hom.:

3387

Bravo

AF:

0.228

Asia WGS

AF:

0.262

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.57

(source)

DANN

Benign

0.38

PhyloP100

-1.2

Mutation Taster

=99/1

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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rs11227247

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over