rs11227247

Variant names:

• chr11-65655382-A-C
• rs11227247
• ENST00000525693.5:c.*205T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65655382-A-C
• chr11-65655382-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 24 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525693.5. 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
	RELA	NM_021975.4	MANE Select	c.1033+306T>G		intron	N/A	NP_068810.3
	RELA	NM_001404657.1		c.1066+306T>G		intron	N/A	NP_001391586.1
	RELA	NM_001145138.2		c.1024+306T>G		intron	N/A	NP_001138610.1	Q04206-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELA	ENST00000525693.5	TSL:1	c.*205T>G		3_prime_UTR	Exon 10 of 10	ENSP00000432537.1	Q2TAM5
	RELA	ENST00000406246.8	TSL:1 MANE Select	c.1033+306T>G		intron	N/A	ENSP00000384273.3	Q04206-1
	RELA	ENST00000308639.13	TSL:1	c.1024+306T>G		intron	N/A	ENSP00000311508.9	Q04206-4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30314 AN: 152000 Hom.: 3900 Cov.: 32

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.: 0 AF XY: 0.152 AC XY: 34014 AN XY: 223084

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

GnomAD4 genome AF: 0.199 AC: 30345 AN: 152118 Hom.: 3905 Cov.: 32 AF XY: 0.199 AC XY: 14803 AN XY: 74364

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8318 AN: 67998

Other (OTH) AF: 0.190 AC: 401 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.57
DANN	Benign	0.38
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11227247;

hg19: chr11-65422853;

COSMIC: COSV58016081;

COSMIC: COSV58016081;