2-60881861-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001291746.2(REL):c.10+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,487,866 control chromosomes in the GnomAD database, including 5,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (702 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4472 hom.)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0670

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-60881861-A-T is Benign according to our data. Variant chr2-60881861-A-T is described in ClinVar as [Benign]. Clinvar id is 1970920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REL	NM_001291746.2	c.10+11A>T		intron_variant		ENST00000394479.4
REL	NM_002908.4	c.10+11A>T		intron_variant
REL	XM_017004627.3	c.10+11A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REL	ENST00000394479.4	c.10+11A>T		intron_variant		1	NM_001291746.2	P1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13808 AN: 152024 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.107 AC: 9912 AN: 92414 Hom.: 589 AF XY: 0.111 AC XY: 5633 AN XY: 50600

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.0706

Gnomad NFE exome AF: 0.0808

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0760 AC: 101558 AN: 1335724 Hom.: 4472 Cov.: 30 AF XY: 0.0784 AC XY: 51619 AN XY: 658328

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0658

Gnomad4 OTH exome AF: 0.0883

GnomAD4 genome AF: 0.0908 AC: 13815 AN: 152142 Hom.: 702 Cov.: 32 AF XY: 0.0936 AC XY: 6962 AN XY: 74402

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0515 Hom.: 72

Bravo AF: 0.0955

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.8
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs842650; hg19: chr2-61108996; COSMIC: COSV104400085; COSMIC: COSV104400085;