chr2-60899529-A-G

Position:

• chr2-60899529-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001291746.2(REL):​c.303-1463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,328 control chromosomes in the GnomAD database, including 3,427 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 0.20 (3420 hom., cov: 32)
  • Exomes 𝑓: 0.31 (7 hom.)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REL	NM_001291746.2	c.303-1463A>G		intron_variant		ENST00000394479.4
REL	NM_002908.4	c.303-1463A>G		intron_variant
REL	XM_017004627.3	c.303-1463A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REL	ENST00000394479.4	c.303-1463A>G		intron_variant		1	NM_001291746.2	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30939 AN: 152060 Hom.: 3421 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.313 AC: 47 AN: 150 Hom.: 7 Cov.: 0 AF XY: 0.345 AC XY: 29 AN XY: 84

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.318

Gnomad4 NFE exome AF: 0.286

GnomAD4 genome AF: 0.203 AC: 30945 AN: 152178 Hom.: 3420 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74390

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.240

Alfa AF: 0.235 Hom.: 4535

Bravo AF: 0.192

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.95

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: rs10193964; hg19: chr2-61126664; COSMIC: COSV54362535;