rs12135588

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000699640.1	c.-385+617A>G		intron_variant				ENSP00000514493

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

Gnomad4 AFR AF: 0.00484

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0326

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0182 Hom.: 11

Bravo AF: 0.0179

Asia WGS AF: 0.0160 AC: 57 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12135588; hg19: chr1-207627057;