Variant 2-60891604-A-G 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_001291746.2(REL):c.11-79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,228,658 control chromosomes in the GnomAD database, including 32,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 3949 hom., cov: 32)

Exomes 𝑓: 0.23 ( 28773 hom. )

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

Variant links:

Genes affected

REL (HGNC:9954): (REL proto-oncogene, NF-kB subunit) This gene encodes a protein that belongs to the Rel homology domain/immunoglobulin-like fold, plexin, transcription factor (RHD/IPT) family. Members of this family regulate genes involved in apoptosis, inflammation, the immune response, and oncogenic processes. This proto-oncogene plays a role in the survival and proliferation of B lymphocytes. Mutation or amplification of this gene is associated with B-cell lymphomas, including Hodgkin's lymphoma. Single nucleotide polymorphisms in this gene are associated with susceptibility to ulcerative colitis and rheumatoid arthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

REL 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=-0.85).

BP6

Variant 2-60891604-A-G is Benign according to our data. Variant chr2-60891604-A-G is described in ClinVar as [Benign]. Clinvar id is 2688308.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
REL	NM_001291746.2 linkuse as main transcript	c.11-79A>G	intron_variant	ENST00000394479.4
REL	NM_002908.4 linkuse as main transcript	c.11-79A>G	intron_variant
REL	XM_017004627.3 linkuse as main transcript	c.11-79A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REL	ENST00000394479.4 linkuse as main transcript	c.11-79A>G		intron_variant		1	NM_001291746.2	P1	Q04864-2

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33966

AN:

151864

Hom.:

3945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.00925

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.226

AC:

243650

AN:

1076676

Hom.:

28773

AF XY:

0.225

AC XY:

119551

AN XY:

531360

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.00563

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.225

GnomAD4 genome

AF:

0.224

AC:

33996

AN:

151982

Hom.:

3949

Cov.:

AF XY:

0.221

AC XY:

16450

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.00927

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.190

Hom.:

718

Bravo

AF:

0.214

Asia WGS

AF:

0.0830

AC:

289

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.074

DANN

Benign

0.67

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