rs34695944

Variant names:

• chr2-60897715-T-C
• rs34695944
• NM_001291746.2:c.302+3170T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291746.2(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 NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 47 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 92

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
REL	NM_001291746.2	c.302+3170T>C		intron_variant	Intron 3 of 9	ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.302+3170T>C		intron_variant	Intron 3 of 10		NP_002899.1
REL	NM_001438025.1	c.302+3170T>C		intron_variant	Intron 3 of 8		NP_001424954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.302+3170T>C		intron_variant	Intron 3 of 9	1	NM_001291746.2	ENSP00000377989.4

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

African (AFR) AF: 0.100 AC: 4153 AN: 41422

American (AMR) AF: 0.238 AC: 3627 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5174

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3584 AN: 10498

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25244 AN: 67904

Other (OTH) AF: 0.276 AC: 580 AN: 2104

Alfa AF: 0.318 Hom.: 15979

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
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34695944; hg19: chr2-61124850;