rs842644

chr2-60894357-G-Achr2-60894357-G-Cchr2-60894357-G-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.154-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,233,650 control chromosomes in the GnomAD database, including 551,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70101 hom., cov: 32)
  • Exomes 𝑓: 0.94 (481818 hom.)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224

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=-0.91).
• BP6: Variant 2-60894357-G-A is Benign according to our data. Variant chr2-60894357-G-A is described in ClinVar as [Benign]. Clinvar id is 2688192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REL	NM_001291746.2	c.154-40G>A		intron_variant		ENST00000394479.4
REL	NM_002908.4	c.154-40G>A		intron_variant
REL	XM_017004627.3	c.154-40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REL	ENST00000394479.4	c.154-40G>A		intron_variant		1	NM_001291746.2	P1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145965 AN: 152172 Hom.: 70048 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.970

GnomAD3 exomes AF: 0.949 AC: 159389 AN: 167920 Hom.: 75720 AF XY: 0.950 AC XY: 86621 AN XY: 91144

Gnomad AFR exome AF: 0.988

Gnomad AMR exome AF: 0.903

Gnomad ASJ exome AF: 0.972

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.956

Gnomad FIN exome AF: 0.944

Gnomad NFE exome AF: 0.944

Gnomad OTH exome AF: 0.951

GnomAD4 exome AF: 0.944 AC: 1020470 AN: 1081360 Hom.: 481818 Cov.: 13 AF XY: 0.944 AC XY: 507987 AN XY: 537944

Gnomad4 AFR exome AF: 0.991

Gnomad4 AMR exome AF: 0.909

Gnomad4 ASJ exome AF: 0.971

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.951

Gnomad4 FIN exome AF: 0.944

Gnomad4 NFE exome AF: 0.939

Gnomad4 OTH exome AF: 0.955

GnomAD4 genome AF: 0.959 AC: 146077 AN: 152290 Hom.: 70101 Cov.: 32 AF XY: 0.959 AC XY: 71389 AN XY: 74456

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.970

Alfa AF: 0.955 Hom.: 9026

Bravo AF: 0.959

Asia WGS AF: 0.978 AC: 3398 AN: 3474

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.17

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: rs842644; hg19: chr2-61121492;