rs10185028

Variant names:

• chr2-60891604-A-G
• rs10185028
• NM_001291746.2:c.11-79A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-60891604-A-G
• chr2-60891604-A-T

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.11-79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,228,658 control chromosomes in the GnomAD database, including 32,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3949 hom., cov: 32)
  • Exomes 𝑓: 0.23 (28773 hom.)
• Consequence: REL NM_001291746.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67
• Publications: 12 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=-0.85).
• BP6: Variant 2-60891604-A-G is Benign according to our data. Variant chr2-60891604-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688308.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	NM_001291746.2	MANE Select	c.11-79A>G		intron	N/A	NP_001278675.1
	REL	NM_002908.4		c.11-79A>G		intron	N/A	NP_002899.1
	REL	NM_001438025.1		c.11-79A>G		intron	N/A	NP_001424954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REL	ENST00000394479.4	TSL:1 MANE Select	c.11-79A>G		intron	N/A	ENSP00000377989.4
	REL	ENST00000295025.12	TSL:1	c.11-79A>G		intron	N/A	ENSP00000295025.7
	REL	ENST00000699191.1		c.11-79A>G		intron	N/A	ENSP00000514191.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33966 AN: 151864 Hom.: 3945 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.226 AC: 243650 AN: 1076676 Hom.: 28773 AF XY: 0.225 AC XY: 119551 AN XY: 531360

African (AFR) AF: 0.242 AC: 5560 AN: 22978

American (AMR) AF: 0.133 AC: 2790 AN: 20972

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 6085 AN: 16900

East Asian (EAS) AF: 0.00563 AC: 178 AN: 31618

South Asian (SAS) AF: 0.139 AC: 6969 AN: 50234

European-Finnish (FIN) AF: 0.258 AC: 11406 AN: 44134

Middle Eastern (MID) AF: 0.341 AC: 1390 AN: 4078

European-Non Finnish (NFE) AF: 0.237 AC: 199249 AN: 841310

Other (OTH) AF: 0.225 AC: 10023 AN: 44452

GnomAD4 genome AF: 0.224 AC: 33996 AN: 151982 Hom.: 3949 Cov.: 32 AF XY: 0.221 AC XY: 16450 AN XY: 74284

African (AFR) AF: 0.234 AC: 9686 AN: 41438

American (AMR) AF: 0.176 AC: 2688 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3468

East Asian (EAS) AF: 0.00927 AC: 48 AN: 5176

South Asian (SAS) AF: 0.131 AC: 631 AN: 4814

European-Finnish (FIN) AF: 0.277 AC: 2924 AN: 10558

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15936 AN: 67946

Other (OTH) AF: 0.246 AC: 519 AN: 2108

Alfa AF: 0.191 Hom.: 736

Bravo AF: 0.214

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	0.074
DANN	Benign	0.67
PhyloP100		-2.7
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: rs10185028; hg19: chr2-61118739;