Genetic Variant REL:c.11-2577C>G (chr2-60889106-C-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.11-2577C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 150,192 control chromosomes in the GnomAD database, including 3,812 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 ( 3812 hom., cov: 32)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0180

Publications

3 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 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.11-2577C>G	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.11-2577C>G	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.11-2577C>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.11-2577C>G	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.11-2577C>G	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.11-2577C>G	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33329

AN:

150076

Hom.:

3810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.00897

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.374

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.246

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

GnomAD4 genome

AF:

0.222

AC:

33350

AN:

150192

Hom.:

3812

Cov.:

AF XY:

0.220

AC XY:

16134

AN XY:

73348

show subpopulations

African (AFR)

AF:

0.226

AC:

9124

AN:

40396

American (AMR)

AF:

0.177

AC:

2670

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1217

AN:

3398

East Asian (EAS)

AF:

0.00899

AC:

AN:

5118

South Asian (SAS)

AF:

0.123

AC:

582

AN:

4748

European-Finnish (FIN)

AF:

0.279

AC:

2928

AN:

10510

Middle Eastern (MID)

AF:

0.361

AC:

104

AN:

288

European-Non Finnish (NFE)

AF:

0.235

AC:

15925

AN:

67670

Other (OTH)

AF:

0.244

AC:

510

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1373

2746

4119

5492

6865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.0883

Hom.:

138

Bravo

AF:

0.210

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.2

(source)

DANN

Benign

0.80

PhyloP100

0.018

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