rs12021671

Variant names:

• chr1-207484800-A-G
• rs12021671
• NM_001006658.3:c.3189-664A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006658.3(CR2):​c.3189-664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,112 control chromosomes in the GnomAD database, including 25,847 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 0.57 (25847 hom., cov: 33)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.666 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.3189-664A>G		intron	N/A	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.3012-664A>G		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.3189-664A>G		intron	N/A	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.3012-664A>G		intron	N/A	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.2826-664A>G		intron	N/A	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87190 AN: 151994 Hom.: 25835 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.573 AC: 87230 AN: 152112 Hom.: 25847 Cov.: 33 AF XY: 0.575 AC XY: 42725 AN XY: 74356

African (AFR) AF: 0.427 AC: 17708 AN: 41480

American (AMR) AF: 0.677 AC: 10362 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2390 AN: 5184

South Asian (SAS) AF: 0.622 AC: 2997 AN: 4822

European-Finnish (FIN) AF: 0.641 AC: 6775 AN: 10566

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42967 AN: 67982

Other (OTH) AF: 0.589 AC: 1243 AN: 2110

Alfa AF: 0.616 Hom.: 121898

Bravo AF: 0.571

Asia WGS AF: 0.581 AC: 2015 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.85
PhyloP100		-0.78
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: rs12021671; hg19: chr1-207658145;