rs1143665

chr1-207475149-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001006658.3(CR2):c.2649T>C(p.Gly883=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,612,874 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (82 hom.)
• Consequence: CR2 NM_001006658.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0300

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=-0.64).
• BP6: Variant 1-207475149-T-C is Benign according to our data. Variant chr1-207475149-T-C is described in ClinVar as [Benign]. Clinvar id is 439555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.2649T>C	p.Gly883=	synonymous_variant	14/20	ENST00000367057.8
CR2	NM_001877.5	c.2472T>C	p.Gly824=	synonymous_variant	13/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.2649T>C	p.Gly883=	synonymous_variant	14/20	1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3003 AN: 152142 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00570 AC: 1423 AN: 249438 Hom.: 37 AF XY: 0.00422 AC XY: 569 AN XY: 134770

Gnomad AFR exome AF: 0.0741

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00207 AC: 3029 AN: 1460614 Hom.: 82 Cov.: 32 AF XY: 0.00180 AC XY: 1306 AN XY: 726544

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.00406

Gnomad4 ASJ exome AF: 0.000806

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000236

Gnomad4 OTH exome AF: 0.00491

GnomAD4 genome AF: 0.0198 AC: 3010 AN: 152260 Hom.: 93 Cov.: 32 AF XY: 0.0194 AC XY: 1444 AN XY: 74454

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00991 Hom.: 17

Bravo AF: 0.0225

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 7 Benign:2

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	2.2
Dann	Benign	0.61

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: rs1143665; hg19: chr1-207648494;