Variant chr2-60894357-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001291746.2(REL):c.154-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,233,650 control chromosomes in the GnomAD database, including 551,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.96 ( 70101 hom., cov: 32)

Exomes 𝑓: 0.94 ( 481818 hom. )

Consequence

REL
NM_001291746.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-60894357-G-A is Benign according to our data. Variant chr2-60894357-G-A is described in ClinVar as [Benign]. Clinvar id is 2688192.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
REL	NM_001291746.2 linkuse as main transcript	c.154-40G>A	intron_variant	ENST00000394479.4	NP_001278675.1
REL	NM_002908.4 linkuse as main transcript	c.154-40G>A	intron_variant		NP_002899.1
REL	XM_017004627.3 linkuse as main transcript	c.154-40G>A	intron_variant		XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4 linkuse as main transcript	c.154-40G>A		intron_variant		1	NM_001291746.2	ENSP00000377989	P1	Q04864-2

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

145965

AN:

152172

Hom.:

70048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.987

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.928

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.956

Gnomad FIN

AF:

0.951

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.946

Gnomad OTH

AF:

0.970

GnomAD3 exomes

AF:

0.949

AC:

159389

AN:

167920

Hom.:

75720

AF XY:

0.950

AC XY:

86621

AN XY:

91144

show subpopulations

Gnomad AFR exome

AF:

0.988

Gnomad AMR exome

AF:

0.903

Gnomad ASJ exome

AF:

0.972

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.944

Gnomad NFE exome

AF:

0.944

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.944

AC:

1020470

AN:

1081360

Hom.:

481818

Cov.:

AF XY:

0.944

AC XY:

507987

AN XY:

537944

show subpopulations

Gnomad4 AFR exome

AF:

0.991

Gnomad4 AMR exome

AF:

0.909

Gnomad4 ASJ exome

AF:

0.971

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.951

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.939

Gnomad4 OTH exome

AF:

0.955

GnomAD4 genome

AF:

0.959

AC:

146077

AN:

152290

Hom.:

70101

Cov.:

AF XY:

0.959

AC XY:

71389

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.987

Gnomad4 AMR

AF:

0.928

Gnomad4 ASJ

AF:

0.975

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.956

Gnomad4 FIN

AF:

0.951

Gnomad4 NFE

AF:

0.946

Gnomad4 OTH

AF:

0.970

Alfa

AF:

0.955

Hom.:

9026

Bravo

AF:

0.959

Asia WGS

AF:

0.978

AC:

3398

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

DANN

Benign

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over