Genetic Variant REL:c.11-2337A>G (chr2-60889346-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001291746.2(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_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

9 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:

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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=-0.94).

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_001291746.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
REL	NM_001291746.2	MANE Select	c.11-2337A>G	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.11-2337A>G	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.11-2337A>G	intron	N/A	NP_001424954.1	A0A8V8TPL7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
REL	ENST00000394479.4	TSL:1 MANE Select	c.11-2337A>G	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.11-2337A>G	intron	N/A	ENSP00000295025.7	Q04864-1
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.:

show subpopulations

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.:

AF XY:

0.105

AC XY:

7792

AN XY:

74382

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0708

AC:

4815

AN:

68008

Other (OTH)

AF:

0.108

AC:

229

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

708

1416

2125

2833

3541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0845

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

(source)

DANN

Benign

0.27

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over