rs842648

chr2-60889346-A-Gchr2-60889346-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291746.2(REL):c.11-2337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,140 control chromosomes in the GnomAD database, including 964 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (964 hom., cov: 32)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REL	NM_001291746.2	c.11-2337A>G		intron_variant		ENST00000394479.4
REL	NM_002908.4	c.11-2337A>G		intron_variant
REL	XM_017004627.3	c.11-2337A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REL	ENST00000394479.4	c.11-2337A>G		intron_variant		1	NM_001291746.2	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15581 AN: 152022 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15595 AN: 152140 Hom.: 964 Cov.: 32 AF XY: 0.105 AC XY: 7792 AN XY: 74382

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0830 Hom.: 166

Bravo AF: 0.108

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.1
Dann	Benign	0.27

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: rs842648; hg19: chr2-61116481;