chr1-207473578-G-A

Position:

chr1-207473578-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000367057.8(CR2):c.2012G>A(p.Arg671His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,611,296 control chromosomes in the GnomAD database, including 76,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R671C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.30 ( 7231 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68777 hom. )

Consequence

CR2
ENST00000367057.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.15

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.750954E-4).

BP6

Variant 1-207473578-G-A is Benign according to our data. Variant chr1-207473578-G-A is described in ClinVar as [Benign]. Clinvar id is 402561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207473578-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR2	NM_001006658.3 linkuse as main transcript	c.2012G>A	p.Arg671His	missense_variant	11/20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5 linkuse as main transcript	c.1979-223G>A		intron_variant			NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 linkuse as main transcript	c.2012G>A	p.Arg671His	missense_variant	11/20	1	NM_001006658.3	ENSP00000356024	P1	P20023-3

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45751

AN:

151956

Hom.:

7219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.260

AC:

65155

AN:

251076

Hom.:

9223

AF XY:

0.260

AC XY:

35331

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.301

AC:

439033

AN:

1459222

Hom.:

68777

Cov.:

AF XY:

0.299

AC XY:

216775

AN XY:

726054

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.301

AC:

45797

AN:

152074

Hom.:

7231

Cov.:

AF XY:

0.294

AC XY:

21865

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.277

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.307

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.302

Hom.:

17501

Bravo

AF:

0.305

TwinsUK

AF:

0.318

AC:

1178

ALSPAC

AF:

0.325

AC:

1251

ESP6500AA

AF:

0.379

AC:

1672

ESP6500EA

AF:

0.315

AC:

2707

ExAC

AF:

0.268

AC:

32589

Asia WGS

AF:

0.179

AC:

622

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.307

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. 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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.043

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.45

MetaRNN

Benign

0.00058

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.61

REVEL

Benign

0.25

Sift

Benign

0.19

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.13

MPC

0.69

ClinPred

0.039

GERP RS

-8.6

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over