rs61759494

chr1-207468705-C-Achr1-207468705-C-Gchr1-207468705-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001006658.3(CR2):c.624C>A(p.Pro208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,613,986 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P208P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: CR2 NM_001006658.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.81

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-207468705-C-A is Benign according to our data. Variant chr1-207468705-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 473101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207468705-C-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00163 (248/152252) while in subpopulation NFE AF= 0.00226 (154/68008). AF 95% confidence interval is 0.00197. There are 1 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.624C>A	p.Pro208=	synonymous_variant	3/20	ENST00000367057.8
CR2	NM_001877.5	c.624C>A	p.Pro208=	synonymous_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.624C>A	p.Pro208=	synonymous_variant	3/20	1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00228 AC: 573 AN: 251408 Hom.: 2 AF XY: 0.00225 AC XY: 306 AN XY: 135878

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00154

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00268

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00263 AC: 3839 AN: 1461734 Hom.: 8 Cov.: 33 AF XY: 0.00257 AC XY: 1871 AN XY: 727166

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00155

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00272

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152252 Hom.: 1 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74452

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00243 Hom.: 0

Bravo AF: 0.00188

EpiCase AF: 0.00311

EpiControl AF: 0.00433

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 09, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	CR2: BP4, BP7 -

Immunodeficiency, common variable, 7 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

CR2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.66
Dann	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs61759494; hg19: chr1-207642050;