2-60889346-A-G

Variant names:

• chr2-60889346-A-G
• rs842648
• NM_001291746.2:c.11-2337A>G

Variant summary

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

The NM_002908.4(REL):​c.11-2337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,140 control chromosomes in the GnomAD database, including 964 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 0.10 (964 hom., cov: 32)
• Consequence: REL NM_002908.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002908.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	NM_001291746.2	MANE Select	c.11-2337A>G		intron	N/A	NP_001278675.1
	REL	NM_002908.4		c.11-2337A>G		intron	N/A	NP_002899.1
	REL	NM_001438025.1		c.11-2337A>G		intron	N/A	NP_001424954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	ENST00000394479.4	TSL:1 MANE Select	c.11-2337A>G		intron	N/A	ENSP00000377989.4
	REL	ENST00000295025.12	TSL:1	c.11-2337A>G		intron	N/A	ENSP00000295025.7
	REL	ENST00000949523.1		c.11-2337A>G		intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15581 AN: 152022 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.103 AC: 15595 AN: 152140 Hom.: 964 Cov.: 32 AF XY: 0.105 AC XY: 7792 AN XY: 74382

African (AFR) AF: 0.157 AC: 6500 AN: 41476

American (AMR) AF: 0.107 AC: 1638 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.106 AC: 551 AN: 5184

South Asian (SAS) AF: 0.121 AC: 582 AN: 4814

European-Finnish (FIN) AF: 0.0683 AC: 723 AN: 10592

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4815 AN: 68008

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.0845 Hom.: 173

Bravo AF: 0.108

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.27
PhyloP100		0.086
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: rs842648; hg19: chr2-61116481; COSMIC: COSV107324937;