2-60889106-C-G

Variant names:

• chr2-60889106-C-G
• rs13422089
• NM_001291746.2:c.11-2577C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001291746.2(REL):​c.11-2577C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 150,192 control chromosomes in the GnomAD database, including 3,812 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 0.22 (3812 hom., cov: 32)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REL	NM_001291746.2	c.11-2577C>G		intron_variant	Intron 1 of 9	ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.11-2577C>G		intron_variant	Intron 1 of 10		NP_002899.1
REL	NM_001438025.1	c.11-2577C>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.11-2577C>G		intron_variant	Intron 1 of 9	1	NM_001291746.2	ENSP00000377989.4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33329 AN: 150076 Hom.: 3810 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.00897

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.222 AC: 33350 AN: 150192 Hom.: 3812 Cov.: 32 AF XY: 0.220 AC XY: 16134 AN XY: 73348

African (AFR) AF: 0.226 AC: 9124 AN: 40396

American (AMR) AF: 0.177 AC: 2670 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1217 AN: 3398

East Asian (EAS) AF: 0.00899 AC: 46 AN: 5118

South Asian (SAS) AF: 0.123 AC: 582 AN: 4748

European-Finnish (FIN) AF: 0.279 AC: 2928 AN: 10510

Middle Eastern (MID) AF: 0.361 AC: 104 AN: 288

European-Non Finnish (NFE) AF: 0.235 AC: 15925 AN: 67670

Other (OTH) AF: 0.244 AC: 510 AN: 2088

Alfa AF: 0.0883 Hom.: 138

Bravo AF: 0.210

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		0.018
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: rs13422089; hg19: chr2-61116241;