rs10185028

chr2-60891604-A-Gchr2-60891604-A-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
REL	NM_001291746.2	c.11-79A>G		intron_variant		ENST00000394479.4
REL	NM_002908.4	c.11-79A>G		intron_variant
REL	XM_017004627.3	c.11-79A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33966 AN: 151864 Hom.: 3945 Cov.: 32

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

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.: 32 AF XY: 0.221 AC XY: 16450 AN XY: 74284

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

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

Other links and lift over

dbSNP: rs10185028; hg19: chr2-61118739;