Genetic Variant NM_001291746.2:c.302+3170T>C (chr2-60897715-T-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.302+3170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,822 control chromosomes in the GnomAD database, including 6,295 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 0.26 ( 6295 hom., cov: 30)

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Publications

47 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 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.302+3170T>C	intron	N/A	NP_001278675.1	Q04864-2
REL	NM_002908.4		c.302+3170T>C	intron	N/A	NP_002899.1	Q04864-1
REL	NM_001438025.1		c.302+3170T>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.302+3170T>C	intron	N/A	ENSP00000377989.4	Q04864-2
REL	ENST00000295025.12	TSL:1	c.302+3170T>C	intron	N/A	ENSP00000295025.7	Q04864-1
REL	ENST00000949523.1		c.302+3170T>C	intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39106

AN:

151704

Hom.:

6298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.0201

Gnomad SAS

AF:

0.0870

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.280

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

GnomAD4 genome

AF:

0.258

AC:

39097

AN:

151822

Hom.:

6295

Cov.:

AF XY:

0.250

AC XY:

18580

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.100

AC:

4153

AN:

41422

American (AMR)

AF:

0.238

AC:

3627

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1012

AN:

3470

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5174

South Asian (SAS)

AF:

0.0871

AC:

420

AN:

4824

European-Finnish (FIN)

AF:

0.341

AC:

3584

AN:

10498

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.372

AC:

25244

AN:

67904

Other (OTH)

AF:

0.276

AC:

580

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1366

2731

4097

5462

6828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.318

Hom.:

15979

Bravo

AF:

0.246

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.7

(source)

DANN

Benign

0.61

PhyloP100

1.8

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