rs11568300

Variant names:

• chr11-65657696-C-G
• rs11568300
• NM_021975.4:c.877+591G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RELA	NM_021975.4	c.877+591G>C		intron_variant	Intron 8 of 10	ENST00000406246.8	NP_068810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246.8	c.877+591G>C		intron_variant	Intron 8 of 10	1	NM_021975.4	ENSP00000384273.3

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

African (AFR) AF: 0.337 AC: 14007 AN: 41520

American (AMR) AF: 0.258 AC: 3943 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1099 AN: 5180

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4824

European-Finnish (FIN) AF: 0.496 AC: 5252 AN: 10582

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24567 AN: 67992

Other (OTH) AF: 0.333 AC: 704 AN: 2114

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
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11568300; hg19: chr11-65425167;