2-60914480-G-C

Position:

• chr2-60914480-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REL	NM_001291746.2	c.395-2397G>C		intron_variant		ENST00000394479.4	NP_001278675.1
REL	NM_002908.4	c.395-2397G>C		intron_variant			NP_002899.1
REL	XM_011533010.4	c.101-2397G>C		intron_variant			XP_011531312.1
REL	XM_017004627.3	c.395-2397G>C		intron_variant			XP_016860116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REL	ENST00000394479.4	c.395-2397G>C		intron_variant		1	NM_001291746.2	ENSP00000377989	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33050 AN: 151826 Hom.: 3799 Cov.: 32

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.: 32 AF XY: 0.216 AC XY: 16020 AN XY: 74274

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.00888

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.247

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.6
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs9309331; hg19: chr2-61141615;