rs1876453

Variant names:

• chr1-207454573-G-A
• rs1876453
• NM_001006658.3:c.58+97G>A

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.0990
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006658.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	NM_001006658.3	MANE Select	c.58+97G>A		intron	N/A	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.58+97G>A		intron	N/A	NP_001868.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	ENST00000367057.8	TSL:1 MANE Select	c.58+97G>A		intron	N/A	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.58+97G>A		intron	N/A	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.58+97G>A		intron	N/A	ENSP00000356026.3	Q5SR47

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

African (AFR) AF: 0.0736 AC: 1348 AN: 18320

American (AMR) AF: 0.0459 AC: 1022 AN: 22258

Ashkenazi Jewish (ASJ) AF: 0.0561 AC: 892 AN: 15898

East Asian (EAS) AF: 0.000257 AC: 8 AN: 31178

South Asian (SAS) AF: 0.0562 AC: 3164 AN: 56302

European-Finnish (FIN) AF: 0.0694 AC: 2141 AN: 30866

Middle Eastern (MID) AF: 0.0439 AC: 173 AN: 3944

European-Non Finnish (NFE) AF: 0.109 AC: 63910 AN: 585068

Other (OTH) AF: 0.0811 AC: 3043 AN: 37524

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

African (AFR) AF: 0.0770 AC: 3198 AN: 41550

American (AMR) AF: 0.0573 AC: 877 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4830

European-Finnish (FIN) AF: 0.0606 AC: 643 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7254 AN: 68008

Other (OTH) AF: 0.0676 AC: 143 AN: 2116

Alfa AF: 0.0924 Hom.: 99

Bravo AF: 0.0808

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency, common variable, 7 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.0
DANN	Benign	0.77
PhyloP100		-0.099
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1876453; hg19: chr1-207627918;