chr11-65653646-G-C

Position:

• chr11-65653646-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021975.4(RELA):​c.*732C>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 0.0488 in 152,598 control chromosomes in the GnomAD database, including 289 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 0.049 (289 hom., cov: 33)
  • Exomes 𝑓: 0.066 (0 hom.)
• Consequence: RELA NM_021975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELA	NM_021975.4	c.*732C>G		3_prime_UTR_variant	11/11	ENST00000406246.8	NP_068810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246	c.*732C>G		3_prime_UTR_variant	11/11	1	NM_021975.4	ENSP00000384273.3

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7429 AN: 152162 Hom.: 289 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0660 AC: 21 AN: 318 Hom.: 0 Cov.: 0 AF XY: 0.0470 AC XY: 11 AN XY: 234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0465

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0488 AC: 7429 AN: 152280 Hom.: 289 Cov.: 33 AF XY: 0.0528 AC XY: 3931 AN XY: 74448

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0534 Hom.: 36

Bravo AF: 0.0368

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.92

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: rs1049728; hg19: chr11-65421117;