rs12135588

Variant names:

• chr1-207453712-A-G
• rs12135588
• ENST00000699640.1:c.-385+617A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-207453712-A-G
• chr1-207453712-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000699640.1(CR2):​c.-385+617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 152,122 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.022 (45 hom., cov: 32)
• Consequence: CR2 ENST00000699640.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0219 (3334/152122) while in subpopulation SAS AF = 0.0326 (157/4818). AF 95% confidence interval is 0.0295. There are 45 homozygotes in GnomAd4. There are 1724 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 Unknown,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699640.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	ENST00000699640.1		c.-385+617A>G		intron	N/A	ENSP00000514493.1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3338 AN: 152004 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0219 AC: 3334 AN: 152122 Hom.: 45 Cov.: 32 AF XY: 0.0232 AC XY: 1724 AN XY: 74390

African (AFR) AF: 0.00484 AC: 201 AN: 41536

American (AMR) AF: 0.0122 AC: 186 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0326 AC: 157 AN: 4818

European-Finnish (FIN) AF: 0.0523 AC: 550 AN: 10512

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0306 AC: 2080 AN: 67990

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0186 Hom.: 15

Bravo AF: 0.0179

Asia WGS AF: 0.0160 AC: 57 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		-0.080

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12135588; hg19: chr1-207627057;