chr2-60894357-G-A

Variant names:

• chr2-60894357-G-A
• rs842644
• NM_001291746.2:c.154-40G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224
• Publications: 13 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	NM_001291746.2	MANE Select	c.154-40G>A		intron	N/A	NP_001278675.1	Q04864-2
	REL	NM_002908.4		c.154-40G>A		intron	N/A	NP_002899.1	Q04864-1
	REL	NM_001438025.1		c.154-40G>A		intron	N/A	NP_001424954.1	A0A8V8TPL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	ENST00000394479.4	TSL:1 MANE Select	c.154-40G>A		intron	N/A	ENSP00000377989.4	Q04864-2
	REL	ENST00000295025.12	TSL:1	c.154-40G>A		intron	N/A	ENSP00000295025.7	Q04864-1
	REL	ENST00000949523.1		c.154-40G>A		intron	N/A	ENSP00000619582.1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145965 AN: 152172 Hom.: 70048 Cov.: 32

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

GnomAD2 exomes AF: 0.949 AC: 159389 AN: 167920 AF XY: 0.950

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 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.: 13 AF XY: 0.944 AC XY: 507987 AN XY: 537944

African (AFR) AF: 0.991 AC: 23235 AN: 23452

American (AMR) AF: 0.909 AC: 22906 AN: 25194

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 17819 AN: 18352

East Asian (EAS) AF: 1.00 AC: 33660 AN: 33676

South Asian (SAS) AF: 0.951 AC: 49807 AN: 52350

European-Finnish (FIN) AF: 0.944 AC: 44859 AN: 47534

Middle Eastern (MID) AF: 0.967 AC: 4101 AN: 4242

European-Non Finnish (NFE) AF: 0.939 AC: 780420 AN: 830844

Other (OTH) AF: 0.955 AC: 43663 AN: 45716

GnomAD4 genome AF: 0.959 AC: 146077 AN: 152290 Hom.: 70101 Cov.: 32 AF XY: 0.959 AC XY: 71389 AN XY: 74456

African (AFR) AF: 0.987 AC: 41051 AN: 41572

American (AMR) AF: 0.928 AC: 14178 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5192

South Asian (SAS) AF: 0.956 AC: 4618 AN: 4830

European-Finnish (FIN) AF: 0.951 AC: 10089 AN: 10608

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64363 AN: 68014

Other (OTH) AF: 0.970 AC: 2047 AN: 2110

Alfa AF: 0.953 Hom.: 28913

Bravo AF: 0.959

Asia WGS AF: 0.978 AC: 3398 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.17
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs842644; hg19: chr2-61121492;