dbSNP rs13031237: REL:c.395-7883G>T (chr2-60908994-G-T) – 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.395-7883G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,098 control chromosomes in the GnomAD database, including 6,086 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 0.25 ( 6086 hom., cov: 32)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.160

Publications

83 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 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.395-7883G>T	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.395-7883G>T	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.395-7883G>T	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.395-7883G>T	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.395-7883G>T	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.395-7883G>T	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38198

AN:

151980

Hom.:

6089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.0785

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.273

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

GnomAD4 genome

AF:

0.251

AC:

38186

AN:

152098

Hom.:

6086

Cov.:

AF XY:

0.245

AC XY:

18199

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0897

AC:

3727

AN:

41538

American (AMR)

AF:

0.233

AC:

3555

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

997

AN:

3472

East Asian (EAS)

AF:

0.0203

AC:

105

AN:

5184

South Asian (SAS)

AF:

0.0784

AC:

378

AN:

4822

European-Finnish (FIN)

AF:

0.340

AC:

3589

AN:

10552

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24899

AN:

67942

Other (OTH)

AF:

0.269

AC:

567

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1360

2721

4081

5442

6802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.321

Hom.:

29542

Bravo

AF:

0.239

Asia WGS

AF:

0.0550

AC:

190

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.36

(source)

DANN

Benign

0.46

PhyloP100

-0.16

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