chr1-207454489-G-A

Variant names:

• chr1-207454489-G-A
• rs373721952
• NM_001006658.3:c.58+13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.589
• Publications: 0 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 -20 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 Unknown,AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.58+13G>A		intron_variant	Intron 1 of 19	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.58+13G>A		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.58+13G>A		intron_variant	Intron 1 of 19	1	NM_001006658.3	ENSP00000356024.3

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

GnomAD2 exomes AF: 0.00418 AC: 731 AN: 174978 AF XY: 0.00563

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 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

African (AFR) AF: 0.0000323 AC: 1 AN: 30974

American (AMR) AF: 0.000198 AC: 8 AN: 40306

Ashkenazi Jewish (ASJ) AF: 0.0000854 AC: 2 AN: 23428

East Asian (EAS) AF: 0.0000536 AC: 2 AN: 37348

South Asian (SAS) AF: 0.0297 AC: 2352 AN: 79290

European-Finnish (FIN) AF: 0.0000527 AC: 2 AN: 37958

Middle Eastern (MID) AF: 0.00772 AC: 43 AN: 5570

European-Non Finnish (NFE) AF: 0.000121 AC: 131 AN: 1079698

Other (OTH) AF: 0.00183 AC: 106 AN: 57890

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

African (AFR) AF: 0.0000963 AC: 4 AN: 41542

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0316 AC: 152 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2110

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 7 Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		-0.59
PromoterAI		-0.052	Neutral
Mutation Taster		=100/0	polymorphism

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: rs373721952; hg19: chr1-207627834;