rs17045328

Variant names:

• chr1-207478831-A-G
• rs17045328
• NM_001006658.3:c.3089-426A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-207478831-A-G
• chr1-207478831-A-T

Variant summary

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

The NM_001006658.3(CR2):​c.3089-426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,176 control chromosomes in the GnomAD database, including 282 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 0.037 (282 hom., cov: 32)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 24 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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.3089-426A>G		intron	N/A	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.2912-426A>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.3089-426A>G		intron	N/A	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.2912-426A>G		intron	N/A	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.2726-426A>G		intron	N/A	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5562 AN: 152058 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0365 AC: 5557 AN: 152176 Hom.: 282 Cov.: 32 AF XY: 0.0390 AC XY: 2902 AN XY: 74390

African (AFR) AF: 0.0280 AC: 1163 AN: 41540

American (AMR) AF: 0.0225 AC: 344 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1444 AN: 5174

South Asian (SAS) AF: 0.0842 AC: 406 AN: 4820

European-Finnish (FIN) AF: 0.0409 AC: 433 AN: 10586

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1655 AN: 67972

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0306 Hom.: 440

Bravo AF: 0.0351

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.89
PhyloP100		0.039
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: rs17045328; hg19: chr1-207652176;