2-60887904-T-G

Variant names:

• chr2-60887904-T-G
• rs10208155
• NM_001291746.2:c.11-3779T>G

Variant summary

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

The NM_001291746.2(REL):​c.11-3779T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,116 control chromosomes in the GnomAD database, including 3,378 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 (3378 hom., cov: 30)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REL	NM_001291746.2	c.11-3779T>G		intron_variant	Intron 1 of 9	ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.11-3779T>G		intron_variant	Intron 1 of 10		NP_002899.1
REL	NM_001438025.1	c.11-3779T>G		intron_variant	Intron 1 of 8		NP_001424954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.11-3779T>G		intron_variant	Intron 1 of 9	1	NM_001291746.2	ENSP00000377989.4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31082 AN: 151000 Hom.: 3377 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.00899

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.206 AC: 31097 AN: 151116 Hom.: 3378 Cov.: 30 AF XY: 0.204 AC XY: 15042 AN XY: 73816

African (AFR) AF: 0.176 AC: 7257 AN: 41246

American (AMR) AF: 0.169 AC: 2563 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1214 AN: 3458

East Asian (EAS) AF: 0.00901 AC: 46 AN: 5106

South Asian (SAS) AF: 0.119 AC: 569 AN: 4782

European-Finnish (FIN) AF: 0.273 AC: 2814 AN: 10306

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15802 AN: 67714

Other (OTH) AF: 0.231 AC: 484 AN: 2096

Alfa AF: 0.119 Hom.: 202

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-1.2
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: rs10208155; hg19: chr2-61115039;