1-207489567-T-C

Variant names:

• chr1-207489567-T-C
• rs9429940
• NM_001006658.3:c.*444T>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.*444T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,216 control chromosomes in the GnomAD database, including 58,527 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 0.88 (58526 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CR2 NM_001006658.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 24 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006658.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	NM_001006658.3	MANE Select	c.*444T>C		3_prime_UTR	Exon 20 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.*444T>C		3_prime_UTR	Exon 19 of 19	NP_001868.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	ENST00000367057.8	TSL:1 MANE Select	c.*444T>C		3_prime_UTR	Exon 20 of 20	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.*444T>C		3_prime_UTR	Exon 19 of 19	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.*444T>C		3_prime_UTR	Exon 18 of 18	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133309 AN: 152096 Hom.: 58489 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.873

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.876 AC: 133401 AN: 152214 Hom.: 58526 Cov.: 32 AF XY: 0.877 AC XY: 65268 AN XY: 74412

African (AFR) AF: 0.866 AC: 35977 AN: 41534

American (AMR) AF: 0.894 AC: 13666 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3472

East Asian (EAS) AF: 0.960 AC: 4980 AN: 5186

South Asian (SAS) AF: 0.954 AC: 4599 AN: 4820

European-Finnish (FIN) AF: 0.854 AC: 9043 AN: 10586

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59183 AN: 68004

Other (OTH) AF: 0.873 AC: 1846 AN: 2114

Alfa AF: 0.873 Hom.: 92136

Bravo AF: 0.878

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.39
PhyloP100		-0.60
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: rs9429940; hg19: chr1-207662912;