2-60885417-G-T

Variant names:

• chr2-60885417-G-T
• rs6545835
• NM_001291746.2:c.10+3567G>T

Variant summary

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

The NM_001291746.2(REL):​c.10+3567G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,988 control chromosomes in the GnomAD database, including 3,631 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 (3631 hom., cov: 32)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 12 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=-0.9).
• 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.10+3567G>T		intron_variant	Intron 1 of 9	ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.10+3567G>T		intron_variant	Intron 1 of 10		NP_002899.1
REL	NM_001438025.1	c.10+3567G>T		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.10+3567G>T		intron_variant	Intron 1 of 9	1	NM_001291746.2	ENSP00000377989.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32584 AN: 151870 Hom.: 3629 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.215 AC: 32604 AN: 151988 Hom.: 3631 Cov.: 32 AF XY: 0.212 AC XY: 15749 AN XY: 74266

African (AFR) AF: 0.209 AC: 8683 AN: 41490

American (AMR) AF: 0.170 AC: 2592 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3466

East Asian (EAS) AF: 0.00887 AC: 46 AN: 5188

South Asian (SAS) AF: 0.118 AC: 567 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2912 AN: 10530

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15835 AN: 67910

Other (OTH) AF: 0.236 AC: 497 AN: 2104

Alfa AF: 0.224 Hom.: 4600

Bravo AF: 0.205

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		0.0010
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: rs6545835; hg19: chr2-61112552;