rs732072

Variant names:

• chr11-65660097-G-A
• rs732072
• NM_021975.4:c.427+27C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-65660097-G-A
• chr11-65660097-G-C
• chr11-65660097-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.85).
• 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 rank	MANE	Protein	UniProt
RELA	NM_021975.4	c.427+27C>T		intron_variant	Intron 5 of 10	ENST00000406246.8	NP_068810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELA	ENST00000406246.8	c.427+27C>T		intron_variant	Intron 5 of 10	1	NM_021975.4	ENSP00000384273.3

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

GnomAD2 exomes AF: 0.0765 AC: 19205 AN: 250988 AF XY: 0.0831

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 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

African (AFR) AF: 0.0129 AC: 428 AN: 33202

American (AMR) AF: 0.0465 AC: 2079 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 1971 AN: 26016

East Asian (EAS) AF: 0.0402 AC: 1591 AN: 39608

South Asian (SAS) AF: 0.165 AC: 14177 AN: 85954

European-Finnish (FIN) AF: 0.0707 AC: 3775 AN: 53404

Middle Eastern (MID) AF: 0.116 AC: 664 AN: 5736

European-Non Finnish (NFE) AF: 0.0750 AC: 82405 AN: 1098422

Other (OTH) AF: 0.0816 AC: 4886 AN: 59842

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

African (AFR) AF: 0.0136 AC: 565 AN: 41536

American (AMR) AF: 0.0605 AC: 926 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.0334 AC: 173 AN: 5174

South Asian (SAS) AF: 0.170 AC: 823 AN: 4828

European-Finnish (FIN) AF: 0.0672 AC: 712 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5379 AN: 67994

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0643 Hom.: 160

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
PhyloP100		0.087
PromoterAI		-0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs732072; hg19: chr11-65427568;