rs147378770

Positions:

• chr1-207471052-T-C

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.1458T>C​(p.Phe486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,662 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: CR2 NM_001006658.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.766

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=-0.88).
• BP6: Variant 1-207471052-T-C is Benign according to our data. Variant chr1-207471052-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 473094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207471052-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.766 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00132 (1932/1461430) while in subpopulation NFE AF= 0.00165 (1832/1111792). AF 95% confidence interval is 0.00158. There are 1 homozygotes in gnomad4_exome. There are 973 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.1458T>C	p.Phe486=	synonymous_variant	8/20	ENST00000367057.8
CR2	NM_001877.5	c.1458T>C	p.Phe486=	synonymous_variant	8/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.1458T>C	p.Phe486=	synonymous_variant	8/20	1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152232 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000828 AC: 206 AN: 248768 Hom.: 0 AF XY: 0.000884 AC XY: 119 AN XY: 134640

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.00132 AC: 1932 AN: 1461430 Hom.: 1 Cov.: 33 AF XY: 0.00134 AC XY: 973 AN XY: 727016

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000751

Gnomad4 NFE exome AF: 0.00165

Gnomad4 OTH exome AF: 0.000762

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152232 Hom.: 3 Cov.: 32 AF XY: 0.000914 AC XY: 68 AN XY: 74376

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00170

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00131 Hom.: 0

Bravo AF: 0.00102

EpiCase AF: 0.00169

EpiControl AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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	Jan 01, 2023	CR2: BP4, BP7 -

Immunodeficiency, common variable, 7 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147378770; hg19: chr1-207644397;