rs11227247

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RELA	NM_021975.4	c.1033+306T>G		intron_variant		ENST00000406246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELA	ENST00000406246.8	c.1033+306T>G		intron_variant		1	NM_021975.4	P3

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

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.169

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.190

Alfa AF: 0.135 Hom.: 2155

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
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs11227247; hg19: chr11-65422853; COSMIC: COSV58016081; COSMIC: COSV58016081;