rs11820062

Positions:

• chr11-65662465-T-C

Variant summary

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

The NM_021975.4(RELA):​c.8-260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 477,742 control chromosomes in the GnomAD database, including 62,217 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 0.52 (20870 hom., cov: 31)
  • Exomes 𝑓: 0.50 (41347 hom.)
• Consequence: RELA NM_021975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELA	NM_021975.4	c.8-260A>G		intron_variant		ENST00000406246.8	NP_068810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246.8	c.8-260A>G		intron_variant		1	NM_021975.4	ENSP00000384273.3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79002 AN: 151756 Hom.: 20853 Cov.: 31

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.498 AC: 162300 AN: 325868 Hom.: 41347 Cov.: 4 AF XY: 0.496 AC XY: 83140 AN XY: 167644

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.521 AC: 79072 AN: 151874 Hom.: 20870 Cov.: 31 AF XY: 0.526 AC XY: 39043 AN XY: 74218

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.494

Alfa AF: 0.489 Hom.: 17196

Bravo AF: 0.522

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.3
DANN	Benign	0.71

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: rs11820062; hg19: chr11-65429936;