Variant rs2306365 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.118

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
RELA	NM_021975.4 linkuse as main transcript	c.428-78C>T		intron_variant		ENST00000406246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELA	ENST00000406246.8 linkuse as main transcript	c.428-78C>T		intron_variant		1	NM_021975.4	P3	Q04206-1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25723

AN:

152118

Hom.:

2687

Cov.:

show subpopulations

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.:

AF XY:

0.142

AC XY:

95340

AN XY:

669822

show subpopulations

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.:

AF XY:

0.170

AC XY:

12648

AN XY:

74448

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over