NM_021975.4:c.428-78C>T

Variant names:

• chr11-65659875-G-A
• rs2306365
• NM_021975.4:c.428-78C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021975.4(RELA):​c.428-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,512,836 control chromosomes in the GnomAD database, including 20,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2691 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17851 hom.)
• Consequence: RELA NM_021975.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-65659875-G-A is Benign according to our data. Variant chr11-65659875-G-A is described in ClinVar as [Benign]. Clinvar id is 2688241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELA	NM_021975.4	c.428-78C>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.428-78C>T		intron_variant	Intron 5 of 10	1	NM_021975.4	ENSP00000384273.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25723 AN: 152118 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.146 AC: 198364 AN: 1360600 Hom.: 17851 Cov.: 26 AF XY: 0.142 AC XY: 95340 AN XY: 669822

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.0790

Gnomad4 FIN exome AF: 0.0991

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.169 AC: 25736 AN: 152236 Hom.: 2691 Cov.: 32 AF XY: 0.170 AC XY: 12648 AN XY: 74448

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0900

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.160

Alfa AF: 0.109 Hom.: 531

Bravo AF: 0.194

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.76

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: rs2306365; hg19: chr11-65427346; COSMIC: COSV58014165; COSMIC: COSV58014165;