11-65655120-C-T

Variant names:

• chr11-65655120-C-T
• rs7119750
• ENST00000525693.5:c.*467G>A

Variant summary

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

The ENST00000525693.5(RELA):​c.*467G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 784,606 control chromosomes in the GnomAD database, including 12,756 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 0.17 (2742 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10014 hom.)
• Consequence: RELA ENST00000525693.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 27 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=-0.9).
• 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	c.1034-120G>A		intron_variant	Intron 10 of 10	ENST00000406246.8	NP_068810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246.8	c.1034-120G>A		intron_variant	Intron 10 of 10	1	NM_021975.4	ENSP00000384273.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25967 AN: 151964 Hom.: 2739 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.0903

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.151 AC: 95204 AN: 632524 Hom.: 10014 Cov.: 8 AF XY: 0.145 AC XY: 47996 AN XY: 331032

African (AFR) AF: 0.211 AC: 3502 AN: 16616

American (AMR) AF: 0.392 AC: 11235 AN: 28644

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2021 AN: 16530

East Asian (EAS) AF: 0.431 AC: 13915 AN: 32266

South Asian (SAS) AF: 0.0844 AC: 4615 AN: 54690

European-Finnish (FIN) AF: 0.0984 AC: 4369 AN: 44406

Middle Eastern (MID) AF: 0.106 AC: 387 AN: 3644

European-Non Finnish (NFE) AF: 0.124 AC: 50129 AN: 403488

Other (OTH) AF: 0.156 AC: 5031 AN: 32240

GnomAD4 genome AF: 0.171 AC: 25978 AN: 152082 Hom.: 2742 Cov.: 32 AF XY: 0.172 AC XY: 12776 AN XY: 74368

African (AFR) AF: 0.217 AC: 9001 AN: 41456

American (AMR) AF: 0.295 AC: 4508 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1937 AN: 5166

South Asian (SAS) AF: 0.0929 AC: 448 AN: 4822

European-Finnish (FIN) AF: 0.0903 AC: 957 AN: 10600

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8240 AN: 67972

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.154 Hom.: 1434

Bravo AF: 0.196

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.23
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs7119750; hg19: chr11-65422591; COSMIC: COSV58014004; COSMIC: COSV58014004;