chr1-207462444-T-C

Variant names:

• chr1-207462444-T-C
• rs1567190
• NM_001006658.3:c.59-4082T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006658.3(CR2):​c.59-4082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,982 control chromosomes in the GnomAD database, including 15,943 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 0.44 (15943 hom., cov: 32)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.59-4082T>C		intron_variant	Intron 1 of 19	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.59-4082T>C		intron_variant	Intron 1 of 18		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.59-4082T>C		intron_variant	Intron 1 of 19	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66818 AN: 151864 Hom.: 15936 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.440 AC: 66834 AN: 151982 Hom.: 15943 Cov.: 32 AF XY: 0.446 AC XY: 33142 AN XY: 74274

African (AFR) AF: 0.245 AC: 10145 AN: 41472

American (AMR) AF: 0.578 AC: 8813 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2235 AN: 5170

South Asian (SAS) AF: 0.590 AC: 2837 AN: 4812

European-Finnish (FIN) AF: 0.520 AC: 5486 AN: 10560

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33892 AN: 67936

Other (OTH) AF: 0.440 AC: 928 AN: 2108

Alfa AF: 0.484 Hom.: 11566

Bravo AF: 0.433

Asia WGS AF: 0.520 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.76
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1567190; hg19: chr1-207635789;