rs13031237

Positions:

• chr2-60908994-G-T

Variant summary

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

The ENST00000394479.4(REL):​c.395-7883G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,098 control chromosomes in the GnomAD database, including 6,086 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 0.25 (6086 hom., cov: 32)
• Consequence: REL ENST00000394479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REL	NM_001291746.2	c.395-7883G>T		intron_variant		ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.395-7883G>T		intron_variant			NP_002899.1
REL	XM_011533010.4	c.101-7883G>T		intron_variant			XP_011531312.1
REL	XM_017004627.3	c.395-7883G>T		intron_variant			XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.395-7883G>T		intron_variant		1	NM_001291746.2	ENSP00000377989	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38198 AN: 151980 Hom.: 6089 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.251 AC: 38186 AN: 152098 Hom.: 6086 Cov.: 32 AF XY: 0.245 AC XY: 18199 AN XY: 74340

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.0784

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.269

Alfa AF: 0.331 Hom.: 13758

Bravo AF: 0.239

Asia WGS AF: 0.0550 AC: 190 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.46

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: rs13031237; hg19: chr2-61136129;