chr1-207480050-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006658.3(CR2):c.3185C>A(p.Ala1062Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,608,866 control chromosomes in the GnomAD database, including 597,269 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60237 hom., cov: 32)

Exomes 𝑓: 0.86 ( 537032 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.173

Publications

32 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.1627176E-7).

BP6

Variant 1-207480050-C-A is Benign according to our data. Variant chr1-207480050-C-A is described in ClinVar as Benign. ClinVar VariationId is 402562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.3185C>A	p.Ala1062Glu	missense	Exon 18 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.3008C>A	p.Ala1003Glu	missense	Exon 17 of 19	NP_001868.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CR2	ENST00000367057.8	TSL:1 MANE Select	c.3185C>A	p.Ala1062Glu	missense	Exon 18 of 20	ENSP00000356024.3	P20023-3
CR2	ENST00000367058.7	TSL:1	c.3008C>A	p.Ala1003Glu	missense	Exon 17 of 19	ENSP00000356025.3	P20023-1
CR2	ENST00000367059.3	TSL:1	c.2822C>A	p.Ala941Glu	missense	Exon 16 of 18	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134882

AN:

152116

Hom.:

60181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.878

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.926

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.879

GnomAD2 exomes

AF:

0.882

AC:

221217

AN:

250948

AF XY:

0.878

show subpopulations

Gnomad AFR exome

AF:

0.978

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.858

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.858

AC:

1249093

AN:

1456632

Hom.:

537032

Cov.:

AF XY:

0.858

AC XY:

622065

AN XY:

724876

show subpopulations

African (AFR)

AF:

0.979

AC:

32641

AN:

33334

American (AMR)

AF:

0.914

AC:

40822

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.831

AC:

21672

AN:

26082

East Asian (EAS)

AF:

1.00

AC:

39638

AN:

39654

South Asian (SAS)

AF:

0.920

AC:

79323

AN:

86174

European-Finnish (FIN)

AF:

0.858

AC:

45754

AN:

53348

Middle Eastern (MID)

AF:

0.894

AC:

5145

AN:

5756

European-Non Finnish (NFE)

AF:

0.842

AC:

932042

AN:

1107406

Other (OTH)

AF:

0.865

AC:

52056

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

8338

16677

25015

33354

41692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21070

42140

63210

84280

105350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.887

AC:

134997

AN:

152234

Hom.:

60237

Cov.:

AF XY:

0.889

AC XY:

66171

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.972

AC:

40400

AN:

41554

American (AMR)

AF:

0.878

AC:

13422

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

2870

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5183

AN:

5186

South Asian (SAS)

AF:

0.925

AC:

4461

AN:

4824

European-Finnish (FIN)

AF:

0.859

AC:

9100

AN:

10590

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56723

AN:

67998

Other (OTH)

AF:

0.880

AC:

1861

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

754

1508

2263

3017

3771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.851

Hom.:

148673

Bravo

AF:

0.893

TwinsUK

AF:

0.849

AC:

3147

ALSPAC

AF:

0.844

AC:

3251

ESP6500AA

AF:

0.976

AC:

4299

ESP6500EA

AF:

0.829

AC:

7127

ExAC

AF:

0.883

AC:

107250

Asia WGS

AF:

0.967

AC:

3361

AN:

3478

EpiCase

AF:

0.829

EpiControl

AF:

0.840

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency, common variable, 7 (2)

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.81

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.099

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.15

MetaRNN

Benign

7.2e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

PhyloP100

-0.17

PrimateAI

Benign

0.32

PROVEAN

Benign

1.4

REVEL

Benign

0.063

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.064

MPC

0.19

ClinPred

0.00086

GERP RS

-2.1

Varity_R

0.068

gMVP

0.49

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over