rs11568300

chr11-65657696-C-G

Variant summary

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

The NM_021975.4(RELA):c.877+591G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,172 control chromosomes in the GnomAD database, including 9,473 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 0.35 (9473 hom., cov: 32)
• Consequence: RELA NM_021975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELA	NM_021975.4	c.877+591G>C		intron_variant		ENST00000406246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELA	ENST00000406246.8	c.877+591G>C		intron_variant		1	NM_021975.4	P3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52739 AN: 152054 Hom.: 9466 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52784 AN: 152172 Hom.: 9473 Cov.: 32 AF XY: 0.351 AC XY: 26114 AN XY: 74402

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.333

Alfa AF: 0.368 Hom.: 1557

Bravo AF: 0.322

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.4
Dann	Benign	0.39

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: rs11568300; hg19: chr11-65425167;