rs1876453

chr1-207454573-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006658.3(CR2):c.58+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 953,620 control chromosomes in the GnomAD database, including 4,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (563 hom., cov: 32)
  • Exomes 𝑓: 0.094 (4135 hom.)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0990

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-207454573-G-A is Benign according to our data. Variant chr1-207454573-G-A is described in ClinVar as [Benign]. Clinvar id is 1166837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.58+97G>A		intron_variant		ENST00000367057.8
CR2	NM_001877.5	c.58+97G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.58+97G>A		intron_variant		1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12586 AN: 152144 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0678

GnomAD4 exome AF: 0.0945 AC: 75701 AN: 801358 Hom.: 4135 Cov.: 10 AF XY: 0.0928 AC XY: 37434 AN XY: 403490

Gnomad4 AFR exome AF: 0.0736

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.0561

Gnomad4 EAS exome AF: 0.000257

Gnomad4 SAS exome AF: 0.0562

Gnomad4 FIN exome AF: 0.0694

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0827 AC: 12591 AN: 152262 Hom.: 563 Cov.: 32 AF XY: 0.0798 AC XY: 5943 AN XY: 74464

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0924 Hom.: 99

Bravo AF: 0.0808

Asia WGS AF: 0.0350 AC: 120 AN: 3478

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 19, 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

GeneDx

Jun 18, 2021

This variant is associated with the following publications: (PMID: 25180293) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.0
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1876453; hg19: chr1-207627918;