rs732072

chr11-65660097-G-A

Variant summary

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

The NM_021975.4(RELA):c.427+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,599,096 control chromosomes in the GnomAD database, including 5,332 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 0.060 (354 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4978 hom.)
• Consequence: RELA NM_021975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELA	NM_021975.4	c.427+27C>T		intron_variant		ENST00000406246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELA	ENST00000406246.8	c.427+27C>T		intron_variant		1	NM_021975.4	P3

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9113 AN: 152094 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0638

GnomAD3 exomes AF: 0.0765 AC: 19205 AN: 250988 Hom.: 960 AF XY: 0.0831 AC XY: 11266 AN XY: 135644

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.0758

Gnomad EAS exome AF: 0.0338

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.0730

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.0833

GnomAD4 exome AF: 0.0774 AC: 111976 AN: 1446884 Hom.: 4978 Cov.: 29 AF XY: 0.0804 AC XY: 57922 AN XY: 720812

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0465

Gnomad4 ASJ exome AF: 0.0758

Gnomad4 EAS exome AF: 0.0402

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.0707

Gnomad4 NFE exome AF: 0.0750

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome AF: 0.0599 AC: 9116 AN: 152212 Hom.: 354 Cov.: 32 AF XY: 0.0619 AC XY: 4608 AN XY: 74428

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0605

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0685 Hom.: 85

Bravo AF: 0.0537

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.8
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs732072; hg19: chr11-65427568;