chr2-60889106-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The NM_001291746.2(REL):​c.11-2577C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000866 in 150,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000087 (0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000866 (13/150100) while in subpopulation AFR AF = 0.000298 (12/40286). AF 95% confidence interval is 0.000171. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000866 AC: 13 AN: 150100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000866 AC: 13 AN: 150100 Hom.: 0 Cov.: 32 AF XY: 0.0000819 AC XY: 6 AN XY: 73234

African (AFR) AF: 0.000298 AC: 12 AN: 40286

American (AMR) AF: 0.0000665 AC: 1 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67684

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.4
DANN	Benign	0.83
PhyloP100		0.018

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;