1-207466350-C-G

Variant names:

• chr1-207466350-C-G
• rs311311
• NM_001006658.3:c.59-176C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001006658.3(CR2):​c.59-176C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,062 control chromosomes in the GnomAD database, including 34,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (34068 hom., cov: 32)
• Consequence: CR2 NM_001006658.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-207466350-C-G is Benign according to our data. Variant chr1-207466350-C-G is described in ClinVar as [Benign]. Clinvar id is 1226449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.59-176C>G		intron_variant	Intron 1 of 19	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.59-176C>G		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.59-176C>G		intron_variant	Intron 1 of 19	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100320 AN: 151944 Hom.: 34063 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.660 AC: 100357 AN: 152062 Hom.: 34068 Cov.: 32 AF XY: 0.668 AC XY: 49668 AN XY: 74302

African (AFR) AF: 0.491 AC: 20352 AN: 41416

American (AMR) AF: 0.765 AC: 11696 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2504 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4628 AN: 5184

South Asian (SAS) AF: 0.771 AC: 3714 AN: 4814

European-Finnish (FIN) AF: 0.772 AC: 8177 AN: 10590

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46931 AN: 67980

Other (OTH) AF: 0.676 AC: 1427 AN: 2112

Alfa AF: 0.588 Hom.: 1849

Bravo AF: 0.651

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs311311; hg19: chr1-207639695;