chr1-207454472-C-T

Variant names:

• chr1-207454472-C-T
• NM_001006658.3:c.54C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001006658.3(CR2):​c.54C>T​(p.Val18Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CR2 NM_001006658.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 1-207454472-C-T is Benign according to our data. Variant chr1-207454472-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2112836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.

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.54C>T	p.Val18Val	synonymous	Exon 1 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.54C>T	p.Val18Val	synonymous	Exon 1 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.54C>T	p.Val18Val	synonymous	Exon 1 of 20	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.54C>T	p.Val18Val	synonymous	Exon 1 of 19	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.54C>T	p.Val18Val	synonymous	Exon 1 of 18	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414814 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 701694

African (AFR) AF: 0.00 AC: 0 AN: 31456

American (AMR) AF: 0.00 AC: 0 AN: 42072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24530

East Asian (EAS) AF: 0.00 AC: 0 AN: 37668

South Asian (SAS) AF: 0.00 AC: 0 AN: 81964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093728

Other (OTH) AF: 0.00 AC: 0 AN: 58694

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency, common variable, 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		0.024
PromoterAI		0.067	Neutral
Mutation Taster		=100/0	polymorphism

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

hg19: chr1-207627817; COSMIC: COSV65506043; COSMIC: COSV65506043;