chr11-65662465-T-C

Variant names:

• chr11-65662465-T-C
• rs11820062
• NM_021975.4:c.8-260A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELA	NM_021975.4	MANE Select	c.8-260A>G		intron	N/A	NP_068810.3
	RELA	NM_001404657.1		c.8-260A>G		intron	N/A	NP_001391586.1
	RELA	NM_001145138.2		c.8-260A>G		intron	N/A	NP_001138610.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELA	ENST00000406246.8	TSL:1 MANE Select	c.8-260A>G		intron	N/A	ENSP00000384273.3
	RELA	ENST00000308639.13	TSL:1	c.8-260A>G		intron	N/A	ENSP00000311508.9
	RELA	ENST00000612991.4	TSL:1	c.8-260A>G		intron	N/A	ENSP00000483705.1

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

African (AFR) AF: 0.566 AC: 4521 AN: 7986

American (AMR) AF: 0.570 AC: 5756 AN: 10092

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 5237 AN: 10872

East Asian (EAS) AF: 0.591 AC: 14041 AN: 23746

South Asian (SAS) AF: 0.423 AC: 7836 AN: 18536

European-Finnish (FIN) AF: 0.558 AC: 14559 AN: 26096

Middle Eastern (MID) AF: 0.435 AC: 691 AN: 1590

European-Non Finnish (NFE) AF: 0.481 AC: 99370 AN: 206476

Other (OTH) AF: 0.503 AC: 10289 AN: 20474

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

African (AFR) AF: 0.572 AC: 23706 AN: 41428

American (AMR) AF: 0.553 AC: 8449 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1691 AN: 3468

East Asian (EAS) AF: 0.587 AC: 3020 AN: 5142

South Asian (SAS) AF: 0.422 AC: 2035 AN: 4820

European-Finnish (FIN) AF: 0.583 AC: 6159 AN: 10556

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32529 AN: 67872

Other (OTH) AF: 0.494 AC: 1042 AN: 2108

Alfa AF: 0.495 Hom.: 24767

Bravo AF: 0.522

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		0.0070
PromoterAI		-0.049	Neutral
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: rs11820062; hg19: chr11-65429936;