dbSNP rs9309331: REL:c.395-2397G>C (chr2-60914480-G-C) – 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.395-2397G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,942 control chromosomes in the GnomAD database, including 3,802 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 0.22 ( 3802 hom., cov: 32)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.574

Publications

7 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 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.395-2397G>C	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.395-2397G>C	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.395-2397G>C	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.395-2397G>C	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.395-2397G>C	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.395-2397G>C	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33050

AN:

151826

Hom.:

3799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.00886

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.249

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

GnomAD4 genome

AF:

0.218

AC:

33070

AN:

151942

Hom.:

3802

Cov.:

AF XY:

0.216

AC XY:

16020

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.203

AC:

8386

AN:

41380

American (AMR)

AF:

0.178

AC:

2726

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1238

AN:

3466

East Asian (EAS)

AF:

0.00888

AC:

AN:

5182

South Asian (SAS)

AF:

0.131

AC:

633

AN:

4824

European-Finnish (FIN)

AF:

0.278

AC:

2933

AN:

10544

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16234

AN:

67946

Other (OTH)

AF:

0.247

AC:

522

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1340

2680

4020

5360

6700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.120

Hom.:

201

Bravo

AF:

0.207

Asia WGS

AF:

0.0780

AC:

270

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.6

(source)

DANN

Benign

0.60

PhyloP100

0.57

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