1-207468705-C-G

Position:

• chr1-207468705-C-G

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>G​(p.Pro208Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,976 control chromosomes in the GnomAD database, including 140 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 0.0091 (9 hom., cov: 32)
  • Exomes 𝑓: 0.011 (131 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]

CR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-207468705-C-G is Benign according to our data. Variant chr1-207468705-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 439556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00911 (1387/152254) while in subpopulation NFE AF= 0.0118 (800/68008). AF 95% confidence interval is 0.0111. There are 9 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR2	NM_001006658.3	c.624C>G	p.Pro208Pro	synonymous_variant	3/20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.624C>G	p.Pro208Pro	synonymous_variant	3/19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.624C>G	p.Pro208Pro	synonymous_variant	3/20	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes AF: 0.00912 AC: 1387 AN: 152136 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00901 AC: 2264 AN: 251408 Hom.: 22 AF XY: 0.00904 AC XY: 1228 AN XY: 135878

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.0150

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00203

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00961

GnomAD4 exome AF: 0.0114 AC: 16603 AN: 1461722 Hom.: 131 Cov.: 33 AF XY: 0.0111 AC XY: 8097 AN XY: 727162

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00211

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00911 AC: 1387 AN: 152254 Hom.: 9 Cov.: 32 AF XY: 0.00998 AC XY: 743 AN XY: 74454

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00695 Hom.: 0

Bravo AF: 0.00735

EpiCase AF: 0.0115

EpiControl AF: 0.0117

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CR2: BP4, BP7, BS1, BS2 -

Immunodeficiency, common variable, 7 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

CR2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 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). -

Systemic lupus erythematosus, susceptibility to, 9;C3150354:Immunodeficiency, common variable, 2;C3542922:Immunodeficiency, common variable, 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.53
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; COSMIC: COSV100889514; COSMIC: COSV100889514;