rs842647

Positions:

• chr2-60892336-G-A

Variant summary

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

The ENST00000394479.4(REL):​c.153+511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,992 control chromosomes in the GnomAD database, including 29,994 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 0.62 (29994 hom., cov: 33)
• Consequence: REL ENST00000394479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REL	NM_001291746.2	c.153+511G>A		intron_variant		ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.153+511G>A		intron_variant			NP_002899.1
REL	XM_017004627.3	c.153+511G>A		intron_variant			XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.153+511G>A		intron_variant		1	NM_001291746.2	ENSP00000377989	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93466 AN: 151874 Hom.: 29966 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.615 AC: 93537 AN: 151992 Hom.: 29994 Cov.: 33 AF XY: 0.608 AC XY: 45150 AN XY: 74280

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.650

Alfa AF: 0.657 Hom.: 17733

Bravo AF: 0.604

Asia WGS AF: 0.256 AC: 892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.20

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: rs842647; hg19: chr2-61119471;