Genetic Variant REL:c.11-1296G>C (chr2-60890387-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001291746.2(REL):c.11-1296G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 152,216 control chromosomes in the GnomAD database, including 17 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 0.011 ( 17 hom., cov: 32)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0750

Publications

3 publications found

Variant links:

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)

REL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1737/152216) while in subpopulation NFE AF = 0.0181 (1232/68016). AF 95% confidence interval is 0.0173. There are 17 homozygotes in GnomAd4. There are 851 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
REL	NM_001291746.2 link	c.11-1296G>C	intron_variant	Intron 1 of 9	ENST00000394479.4	NP_001278675.1	Q04864-2
REL	NM_002908.4 link	c.11-1296G>C	intron_variant	Intron 1 of 10		NP_002899.1	Q04864-1
REL	NM_001438025.1 link	c.11-1296G>C	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 link	c.11-1296G>C		intron_variant	Intron 1 of 9	1	NM_001291746.2	ENSP00000377989.4		Q04864-2

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1737

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.00861

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

GnomAD4 genome

AF:

0.0114

AC:

1737

AN:

152216

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

851

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00286

AC:

119

AN:

41538

American (AMR)

AF:

0.00693

AC:

106

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00456

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0224

AC:

237

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0181

AC:

1232

AN:

68016

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00958

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.67

(source)

DANN

Benign

0.47

PhyloP100

-0.075

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over