rs17258996

Variant names:

• chr1-207480099-T-A
• rs17258996
• NM_001006658.3:c.3188+46T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006658.3(CR2):​c.3188+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,393,920 control chromosomes in the GnomAD database, including 26,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1976 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24093 hom.)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0200
• Publications: 13 publications found

Genes affected

CR2 (HGNC:2336): (complement C3d receptor 2) This gene encodes a membrane protein, which functions as a receptor for Epstein-Barr virus (EBV) binding on B and T lymphocytes. Genetic variations in this gene are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

CR2 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-207480099-T-A is Benign according to our data. Variant chr1-207480099-T-A is described in ClinVar as Benign. ClinVar VariationId is 1244973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006658.3. 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
	CR2	NM_001006658.3	MANE Select	c.3188+46T>A		intron	N/A	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.3011+46T>A		intron	N/A	NP_001868.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	ENST00000367057.8	TSL:1 MANE Select	c.3188+46T>A		intron	N/A	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.3011+46T>A		intron	N/A	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.2825+46T>A		intron	N/A	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23398 AN: 152068 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.167 AC: 41639 AN: 248916 AF XY: 0.172

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.193 AC: 239969 AN: 1241734 Hom.: 24093 Cov.: 17 AF XY: 0.193 AC XY: 121551 AN XY: 629082

African (AFR) AF: 0.0732 AC: 2085 AN: 28488

American (AMR) AF: 0.117 AC: 5170 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5314 AN: 24744

East Asian (EAS) AF: 0.121 AC: 4683 AN: 38574

South Asian (SAS) AF: 0.165 AC: 13442 AN: 81470

European-Finnish (FIN) AF: 0.163 AC: 8610 AN: 52966

Middle Eastern (MID) AF: 0.246 AC: 1313 AN: 5330

European-Non Finnish (NFE) AF: 0.207 AC: 189343 AN: 912912

Other (OTH) AF: 0.189 AC: 10009 AN: 53014

GnomAD4 genome AF: 0.154 AC: 23400 AN: 152186 Hom.: 1976 Cov.: 32 AF XY: 0.151 AC XY: 11265 AN XY: 74402

African (AFR) AF: 0.0750 AC: 3113 AN: 41534

American (AMR) AF: 0.141 AC: 2159 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5182

South Asian (SAS) AF: 0.166 AC: 798 AN: 4820

European-Finnish (FIN) AF: 0.167 AC: 1775 AN: 10598

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13676 AN: 67972

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.182 Hom.: 483

Bravo AF: 0.150

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17258996; hg19: chr1-207653444; COSMIC: COSV65506636;