rs17615

Positions:

chr1-207473117-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.1916G>A(p.Ser639Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,598 control chromosomes in the GnomAD database, including 76,631 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. S639R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.30 ( 7260 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69371 hom. )

Consequence

CR2
ENST00000367057.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.364

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=6.042719E-4).

BP6

Variant 1-207473117-G-A is Benign according to our data. Variant chr1-207473117-G-A is described in ClinVar as [Benign]. Clinvar id is 402559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207473117-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.1916G>A	p.Ser639Asn	missense_variant	10/20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5 linkuse as main transcript	c.1916G>A	p.Ser639Asn	missense_variant	10/19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 linkuse as main transcript	c.1916G>A	p.Ser639Asn	missense_variant	10/20	1	NM_001006658.3	ENSP00000356024	P1	P20023-3

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45870

AN:

151978

Hom.:

7248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.261

AC:

65486

AN:

251076

Hom.:

9329

AF XY:

0.262

AC XY:

35483

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.387

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:

0.232

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.303

AC:

442132

AN:

1461502

Hom.:

69371

Cov.:

AF XY:

0.300

AC XY:

218196

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.380

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:

0.230

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.302

AC:

45916

AN:

152096

Hom.:

7260

Cov.:

AF XY:

0.295

AC XY:

21934

AN XY:

74348

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:

0.228

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.303

Hom.:

17964

Bravo

AF:

0.305

TwinsUK

AF:

0.320

AC:

1187

ALSPAC

AF:

0.327

AC:

1260

ESP6500AA

AF:

0.380

AC:

1674

ESP6500EA

AF:

0.316

AC:

2714

ExAC

AF:

0.270

AC:

32807

Asia WGS

AF:

0.179

AC:

622

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.308

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.00060

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.25

P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.25

T;T;T

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.087

MPC

0.50

ClinPred

0.020

GERP RS

4.8

Varity_R

0.13

gMVP

0.58

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

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