Genetic Variant REL:c.11-3779T>G (chr2-60887904-T-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.11-3779T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,116 control chromosomes in the GnomAD database, including 3,378 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 ( 3378 hom., cov: 30)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

6 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=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 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.11-3779T>G	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.11-3779T>G	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.11-3779T>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.11-3779T>G	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.11-3779T>G	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.11-3779T>G	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31082

AN:

151000

Hom.:

3377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.00899

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.232

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

GnomAD4 genome

AF:

0.206

AC:

31097

AN:

151116

Hom.:

3378

Cov.:

AF XY:

0.204

AC XY:

15042

AN XY:

73816

show subpopulations

African (AFR)

AF:

0.176

AC:

7257

AN:

41246

American (AMR)

AF:

0.169

AC:

2563

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1214

AN:

3458

East Asian (EAS)

AF:

0.00901

AC:

AN:

5106

South Asian (SAS)

AF:

0.119

AC:

569

AN:

4782

European-Finnish (FIN)

AF:

0.273

AC:

2814

AN:

10306

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.233

AC:

15802

AN:

67714

Other (OTH)

AF:

0.231

AC:

484

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1193

2386

3579

4772

5965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.119

Hom.:

202

Bravo

AF:

0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.34

PhyloP100

-1.2

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