11-65655382-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000525693.5(RELA):​c.*205T>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 0.00000469 in 426,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>A		intron	N/A	NP_068810.3
	RELA	NM_001404657.1		c.1066+306T>A		intron	N/A	NP_001391586.1
	RELA	NM_001145138.2		c.1024+306T>A		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>A		3_prime_UTR	Exon 10 of 10	ENSP00000432537.1	Q2TAM5
	RELA	ENST00000406246.8	TSL:1 MANE Select	c.1033+306T>A		intron	N/A	ENSP00000384273.3	Q04206-1
	RELA	ENST00000308639.13	TSL:1	c.1024+306T>A		intron	N/A	ENSP00000311508.9	Q04206-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000469 AC: 2 AN: 426048 Hom.: 0 Cov.: 0 AF XY: 0.00000448 AC XY: 1 AN XY: 223226

African (AFR) AF: 0.00 AC: 0 AN: 12040

American (AMR) AF: 0.0000623 AC: 1 AN: 16046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13320

East Asian (EAS) AF: 0.0000334 AC: 1 AN: 29964

South Asian (SAS) AF: 0.00 AC: 0 AN: 40458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 258582

Other (OTH) AF: 0.00 AC: 0 AN: 24982

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.26
PhyloP100		-1.2

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;