chr2-60895838-G-A

Position:

• chr2-60895838-G-A

Variant summary

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

The NM_001291746.2(REL):​c.302+1293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,918 control chromosomes in the GnomAD database, including 3,620 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 0.21 (3620 hom., cov: 32)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

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]

REL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REL	NM_001291746.2	c.302+1293G>A		intron_variant		ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.302+1293G>A		intron_variant			NP_002899.1
REL	XM_017004627.3	c.302+1293G>A		intron_variant			XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.302+1293G>A		intron_variant		1	NM_001291746.2	ENSP00000377989.4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32405 AN: 151802 Hom.: 3618 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.00888

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.213 AC: 32427 AN: 151918 Hom.: 3620 Cov.: 32 AF XY: 0.211 AC XY: 15685 AN XY: 74242

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.00890

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.239

Alfa AF: 0.223 Hom.: 1006

Bravo AF: 0.203

Asia WGS AF: 0.0740 AC: 256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.50

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: rs6545836; hg19: chr2-61122973;