dbSNP rs10193964: REL:c.303-1463A>G (chr2-60899529-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001291746.2(REL):c.303-1463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,328 control chromosomes in the GnomAD database, including 3,427 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 0.20 ( 3420 hom., cov: 32)

Exomes 𝑓: 0.31 ( 7 hom. )

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

13 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
REL	NM_001291746.2 link	c.303-1463A>G	intron_variant	Intron 3 of 9	ENST00000394479.4	NP_001278675.1	Q04864-2
REL	NM_002908.4 link	c.303-1463A>G	intron_variant	Intron 3 of 10		NP_002899.1	Q04864-1
REL	NM_001438025.1 link	c.303-1463A>G	intron_variant	Intron 3 of 8		NP_001424954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4 link	c.303-1463A>G		intron_variant	Intron 3 of 9	1	NM_001291746.2	ENSP00000377989.4		Q04864-2

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30939

AN:

152060

Hom.:

3421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.00885

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.313

AC:

AN:

150

Hom.:

Cov.:

AF XY:

0.345

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.318

AC:

AN:

132

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.203

AC:

30945

AN:

152178

Hom.:

3420

Cov.:

AF XY:

0.202

AC XY:

15007

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.150

AC:

6239

AN:

41532

American (AMR)

AF:

0.174

AC:

2664

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1237

AN:

3470

East Asian (EAS)

AF:

0.00887

AC:

AN:

5188

South Asian (SAS)

AF:

0.129

AC:

621

AN:

4832

European-Finnish (FIN)

AF:

0.278

AC:

2936

AN:

10568

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16341

AN:

67986

Other (OTH)

AF:

0.240

AC:

507

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1248

2496

3743

4991

6239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.226

Hom.:

6277

Bravo

AF:

0.192

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over