Genetic Variant REL:c.153+511G>A (chr2-60892336-G-A) – 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.153+511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,992 control chromosomes in the GnomAD database, including 29,994 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 0.62 ( 29994 hom., cov: 33)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.476

Publications

31 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=-1.02).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 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.153+511G>A	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.153+511G>A	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.153+511G>A	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.153+511G>A	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.153+511G>A	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.153+511G>A	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93466

AN:

151874

Hom.:

29966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.657

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

GnomAD4 genome

AF:

0.615

AC:

93537

AN:

151992

Hom.:

29994

Cov.:

AF XY:

0.608

AC XY:

45150

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.601

AC:

24881

AN:

41428

American (AMR)

AF:

0.535

AC:

8176

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2743

AN:

3472

East Asian (EAS)

AF:

0.133

AC:

687

AN:

5184

South Asian (SAS)

AF:

0.340

AC:

1640

AN:

4820

European-Finnish (FIN)

AF:

0.686

AC:

7233

AN:

10538

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

46027

AN:

67970

Other (OTH)

AF:

0.650

AC:

1371

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1769

3538

5308

7077

8846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.649

Hom.:

24047

Bravo

AF:

0.604

Asia WGS

AF:

0.256

AC:

892

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.20

PhyloP100

-0.48

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over