1-207454489-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001006658.3(CR2):c.58+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,544,692 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (74 hom.)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589

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=-0.63).
• BP6: Variant 1-207454489-G-A is Benign according to our data. Variant chr1-207454489-G-A is described in ClinVar as [Benign]. Clinvar id is 1168459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00116 (176/152230) while in subpopulation SAS AF= 0.0316 (152/4816). AF 95% confidence interval is 0.0275. There are 4 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.58+13G>A		intron_variant		ENST00000367057.8
CR2	NM_001877.5	c.58+13G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.58+13G>A		intron_variant		1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 152112 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00418 AC: 731 AN: 174978 Hom.: 19 AF XY: 0.00563 AC XY: 542 AN XY: 96216

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0307

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00190 AC: 2647 AN: 1392462 Hom.: 74 Cov.: 28 AF XY: 0.00277 AC XY: 1907 AN XY: 689460

Gnomad4 AFR exome AF: 0.0000323

Gnomad4 AMR exome AF: 0.000198

Gnomad4 ASJ exome AF: 0.0000854

Gnomad4 EAS exome AF: 0.0000536

Gnomad4 SAS exome AF: 0.0297

Gnomad4 FIN exome AF: 0.0000527

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00183

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152230 Hom.: 4 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74430

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0316

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000557 Hom.: 0

Bravo AF: 0.000310

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency, common variable, 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	13
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs373721952; hg19: chr1-207627834;