rs17258996

chr1-207480099-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001006658.3(CR2):c.3188+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,393,920 control chromosomes in the GnomAD database, including 26,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1976 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24093 hom.)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-207480099-T-A is Benign according to our data. Variant chr1-207480099-T-A is described in ClinVar as [Benign]. Clinvar id is 1244973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.3188+46T>A		intron_variant		ENST00000367057.8
CR2	NM_001877.5	c.3011+46T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.3188+46T>A		intron_variant		1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23398 AN: 152068 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.167 AC: 41639 AN: 248916 Hom.: 3702 AF XY: 0.172 AC XY: 23149 AN XY: 134556

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.193 AC: 239969 AN: 1241734 Hom.: 24093 Cov.: 17 AF XY: 0.193 AC XY: 121551 AN XY: 629082

Gnomad4 AFR exome AF: 0.0732

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.154 AC: 23400 AN: 152186 Hom.: 1976 Cov.: 32 AF XY: 0.151 AC XY: 11265 AN XY: 74402

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.179

Alfa AF: 0.182 Hom.: 483

Bravo AF: 0.150

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.6
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17258996; hg19: chr1-207653444; COSMIC: COSV65506636;