chr1-207473553-T-C

Position:

• chr1-207473553-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006658.3(CR2):​c.1987T>C​(p.Ser663Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,609,678 control chromosomes in the GnomAD database, including 80,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9346 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71153 hom.)
• Consequence: CR2 NM_001006658.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7824769E-4).
• BP6: Variant 1-207473553-T-C is Benign according to our data. Variant chr1-207473553-T-C is described in ClinVar as [Benign]. Clinvar id is 402560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207473553-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR2	NM_001006658.3	c.1987T>C	p.Ser663Pro	missense_variant	11/20	ENST00000367057.8
CR2	NM_001877.5	c.1979-248T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR2	ENST00000367057.8	c.1987T>C	p.Ser663Pro	missense_variant	11/20	1	NM_001006658.3	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50782 AN: 151954 Hom.: 9317 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.318

GnomAD3 exomes AF: 0.270 AC: 67724 AN: 250936 Hom.: 10202 AF XY: 0.269 AC XY: 36476 AN XY: 135618

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.305 AC: 444806 AN: 1457606 Hom.: 71153 Cov.: 39 AF XY: 0.303 AC XY: 219532 AN XY: 725296

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.334 AC: 50863 AN: 152072 Hom.: 9346 Cov.: 32 AF XY: 0.327 AC XY: 24289 AN XY: 74348

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.315

Alfa AF: 0.311 Hom.: 18611

Bravo AF: 0.342

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.326 AC: 1256

ESP6500AA AF: 0.497 AC: 2188

ESP6500EA AF: 0.316 AC: 2716

ExAC AF: 0.281 AC: 34078

Asia WGS AF: 0.193 AC: 669 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.308

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Immunodeficiency, common variable, 7 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.29
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00081	N
LIST_S2	Benign	0.050	T
MetaRNN	Benign	0.00018	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.076
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.069
MPC		0.21
ClinPred		0.0019	T
GERP RS		1.2
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs4308977; hg19: chr1-207646898; COSMIC: COSV65506623; COSMIC: COSV65506623;