rs34695944

Positions:

• chr2-60897715-T-C

Variant summary

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

The ENST00000394479.4(REL):​c.302+3170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,822 control chromosomes in the GnomAD database, including 6,295 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 0.26 (6295 hom., cov: 30)
• Consequence: REL ENST00000394479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REL	NM_001291746.2	c.302+3170T>C		intron_variant		ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.302+3170T>C		intron_variant			NP_002899.1
REL	XM_017004627.3	c.302+3170T>C		intron_variant			XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.302+3170T>C		intron_variant		1	NM_001291746.2	ENSP00000377989	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39106 AN: 151704 Hom.: 6298 Cov.: 30

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.258 AC: 39097 AN: 151822 Hom.: 6295 Cov.: 30 AF XY: 0.250 AC XY: 18580 AN XY: 74212

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.276

Alfa AF: 0.325 Hom.: 2118

Bravo AF: 0.246

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.61

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: rs34695944; hg19: chr2-61124850;