rs2063143

Variant names:

• chr1-207468495-C-T
• rs2063143
• NM_001006658.3:c.446-32C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-207468495-C-T
• chr1-207468495-C-A
• chr1-207468495-C-G

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.446-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,609,610 control chromosomes in the GnomAD database, including 31,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2036 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29483 hom.)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.190
• Publications: 6 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=-0.7).
• BP6: Variant 1-207468495-C-T is Benign according to our data. Variant chr1-207468495-C-T is described in ClinVar as Benign. ClinVar VariationId is 1263891.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.446-32C>T		intron	N/A	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.446-32C>T		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.446-32C>T		intron	N/A	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.446-32C>T		intron	N/A	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.446-32C>T		intron	N/A	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24043 AN: 151976 Hom.: 2035 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.169 AC: 42113 AN: 249188 AF XY: 0.173

Gnomad AFR exome AF: 0.0866

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.197 AC: 287223 AN: 1457516 Hom.: 29483 Cov.: 31 AF XY: 0.197 AC XY: 142892 AN XY: 725212

African (AFR) AF: 0.0859 AC: 2866 AN: 33374

American (AMR) AF: 0.119 AC: 5306 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5709 AN: 26090

East Asian (EAS) AF: 0.121 AC: 4796 AN: 39654

South Asian (SAS) AF: 0.167 AC: 14405 AN: 86124

European-Finnish (FIN) AF: 0.162 AC: 8638 AN: 53160

Middle Eastern (MID) AF: 0.252 AC: 1443 AN: 5736

European-Non Finnish (NFE) AF: 0.210 AC: 232490 AN: 1108522

Other (OTH) AF: 0.192 AC: 11570 AN: 60258

GnomAD4 genome AF: 0.158 AC: 24058 AN: 152094 Hom.: 2036 Cov.: 32 AF XY: 0.156 AC XY: 11574 AN XY: 74348

African (AFR) AF: 0.0898 AC: 3728 AN: 41496

American (AMR) AF: 0.143 AC: 2183 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3472

East Asian (EAS) AF: 0.106 AC: 550 AN: 5186

South Asian (SAS) AF: 0.167 AC: 805 AN: 4818

European-Finnish (FIN) AF: 0.167 AC: 1771 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13661 AN: 67942

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.128 Hom.: 304

Bravo AF: 0.155

Asia WGS AF: 0.130 AC: 453 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	-0.70
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		0.19
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: rs2063143; hg19: chr1-207641840; COSMIC: COSV65506602; COSMIC: COSV65506602;