dbSNP rs17045761: CR2:c.*888G>A (chr1-207490011-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001006658.3(CR2):c.*888G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 151,908 control chromosomes in the GnomAD database, including 317 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 0.058 ( 317 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CR2
NM_001006658.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

4 publications found

Variant links:

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

CR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	NM_001006658.3	MANE Select	c.*888G>A		downstream_gene	N/A	NP_001006659.1
	CR2	NM_001877.5		c.*888G>A		downstream_gene	N/A	NP_001868.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CR2	ENST00000367057.8	TSL:1 MANE Select	c.*888G>A	downstream_gene	N/A	ENSP00000356024.3
CR2	ENST00000367058.7	TSL:1	c.*888G>A	downstream_gene	N/A	ENSP00000356025.3
CR2	ENST00000367059.3	TSL:1	c.*888G>A	downstream_gene	N/A	ENSP00000356026.3

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8859

AN:

151786

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0666

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0927

Gnomad FIN

AF:

0.0675

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.0733

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0583

AC:

8860

AN:

151908

Hom.:

317

Cov.:

AF XY:

0.0608

AC XY:

4509

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.0496

AC:

2057

AN:

41452

American (AMR)

AF:

0.0665

AC:

1015

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

155

AN:

3468

East Asian (EAS)

AF:

0.151

AC:

782

AN:

5164

South Asian (SAS)

AF:

0.0922

AC:

444

AN:

4816

European-Finnish (FIN)

AF:

0.0675

AC:

709

AN:

10496

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0501

AC:

3406

AN:

67946

Other (OTH)

AF:

0.0743

AC:

157

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

418

836

1254

1672

2090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0506

Hom.:

Bravo

AF:

0.0581

Asia WGS

AF:

0.0910

AC:

316

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.4

(source)

DANN

Benign

0.76

PhyloP100

0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over