rs144572703

Positions:

chr1-207475111-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001006658.3(CR2):c.2611G>T(p.Val871Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,612,780 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V871V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 30 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.600

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=0.00687328).

BP6

Variant 1-207475111-G-T is Benign according to our data. Variant chr1-207475111-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 439554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207475111-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0033 (503/152280) while in subpopulation SAS AF= 0.00642 (31/4826). AF 95% confidence interval is 0.00465. There are 2 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR2	NM_001006658.3 linkuse as main transcript	c.2611G>T	p.Val871Leu	missense_variant	14/20	ENST00000367057.8	NP_001006659.1	P20023-3
CR2	NM_001877.5 linkuse as main transcript	c.2434G>T	p.Val812Leu	missense_variant	13/19		NP_001868.2	P20023-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 linkuse as main transcript	c.2611G>T	p.Val871Leu	missense_variant	14/20	1	NM_001006658.3	ENSP00000356024.3		P20023-3

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00429

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00334

AC:

834

AN:

249514

Hom.:

AF XY:

0.00355

AC XY:

478

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.000707

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00665

Gnomad FIN exome

AF:

0.000840

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00526

GnomAD4 exome

AF:

0.00510

AC:

7447

AN:

1460500

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

3731

AN XY:

726466

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00693

Gnomad4 FIN exome

AF:

0.000881

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152280

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00332

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00342

AC:

415

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	CR2: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Immunodeficiency, common variable, 7

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Apr 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.19

T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.012

B;B;B

Vest4

0.25

MutPred

0.61

Loss of catalytic residue at V812 (P = 0.0265);.;Loss of catalytic residue at V812 (P = 0.0265);

MVP

0.48

MPC

0.24

ClinPred

0.0033

GERP RS

0.43

Varity_R

0.056

gMVP

0.61

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