rs1048971

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001006658.3(CR2):c.1776G>A(p.Leu592Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,704 control chromosomes in the GnomAD database, including 112,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16050 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96889 hom. )

Consequence

CR2
NM_001006658.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.522

Publications

40 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-207472977-G-A is Benign according to our data. Variant chr1-207472977-G-A is described in ClinVar as Benign. ClinVar VariationId is 402558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.522 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3 link	c.1776G>A	p.Leu592Leu	synonymous_variant	Exon 10 of 20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5 link	c.1776G>A	p.Leu592Leu	synonymous_variant	Exon 10 of 19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 link	c.1776G>A	p.Leu592Leu	synonymous_variant	Exon 10 of 20	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65232

AN:

151896

Hom.:

16008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.336

AC:

84508

AN:

251168

AF XY:

0.333

show subpopulations

Gnomad AFR exome

AF:

0.704

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.357

AC:

521943

AN:

1461690

Hom.:

96889

Cov.:

AF XY:

0.354

AC XY:

257493

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.705

AC:

23583

AN:

33466

American (AMR)

AF:

0.239

AC:

10690

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

7935

AN:

26134

East Asian (EAS)

AF:

0.228

AC:

9045

AN:

39696

South Asian (SAS)

AF:

0.289

AC:

24952

AN:

86258

European-Finnish (FIN)

AF:

0.308

AC:

16447

AN:

53406

Middle Eastern (MID)

AF:

0.404

AC:

2328

AN:

5766

European-Non Finnish (NFE)

AF:

0.364

AC:

405277

AN:

1111900

Other (OTH)

AF:

0.359

AC:

21686

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

21519

43039

64558

86078

107597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12964

25928

38892

51856

64820

<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:

0.430

AC:

65330

AN:

152014

Hom.:

16050

Cov.:

AF XY:

0.422

AC XY:

31331

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.689

AC:

28553

AN:

41446

American (AMR)

AF:

0.304

AC:

4644

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1015

AN:

3468

East Asian (EAS)

AF:

0.209

AC:

1080

AN:

5174

South Asian (SAS)

AF:

0.287

AC:

1384

AN:

4818

European-Finnish (FIN)

AF:

0.308

AC:

3256

AN:

10586

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24065

AN:

67942

Other (OTH)

AF:

0.425

AC:

897

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1744

3487

5231

6974

8718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.363

Hom.:

12294

Bravo

AF:

0.442

Asia WGS

AF:

0.264

AC:

917

AN:

3478

EpiCase

AF:

0.350

EpiControl

AF:

0.356

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Immunodeficiency, common variable, 7

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.63

(source)

DANN

Benign

0.41

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over