rs17047661

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000651.6(CR1):c.6151A>G(p.Arg2051Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,794 control chromosomes in the GnomAD database, including 14,885 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 7751 hom., cov: 32)

Exomes 𝑓: 0.019 ( 7134 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.459

Publications

59 publications found

Variant links:

Genes affected

CR1 (HGNC:2334): (complement C3b/C4b receptor 1 (Knops blood group)) This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]

CR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7961715E-5).

BP6

Variant 1-207609544-A-G is Benign according to our data. Variant chr1-207609544-A-G is described in ClinVar as Benign. ClinVar VariationId is 3056679.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.6151A>G	p.Arg2051Gly	missense_variant	Exon 37 of 47	ENST00000367049.9	NP_000642.3	P17927E9PDY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 link	c.6151A>G	p.Arg2051Gly	missense_variant	Exon 37 of 47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26575

AN:

152084

Hom.:

7725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0690

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.0460

AC:

11454

AN:

248756

AF XY:

0.0351

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.0320

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0192

AC:

28135

AN:

1461592

Hom.:

7134

Cov.:

AF XY:

0.0168

AC XY:

12238

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.634

AC:

21204

AN:

33458

American (AMR)

AF:

0.0356

AC:

1590

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

294

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00153

AC:

132

AN:

86240

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0411

AC:

237

AN:

5768

European-Non Finnish (NFE)

AF:

0.00184

AC:

2050

AN:

1111830

Other (OTH)

AF:

0.0435

AC:

2626

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

734

1467

2201

2934

3668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.175

AC:

26650

AN:

152202

Hom.:

7751

Cov.:

AF XY:

0.169

AC XY:

12613

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.604

AC:

25030

AN:

41446

American (AMR)

AF:

0.0688

AC:

1053

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00332

AC:

226

AN:

68020

Other (OTH)

AF:

0.129

AC:

272

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

583

1167

1750

2334

2917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0648

Hom.:

7772

Bravo

AF:

0.200

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.571

AC:

2160

ESP6500EA

AF:

0.00328

AC:

ExAC

AF:

0.0549

AC:

6630

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CR1-related disorder

Benign:1

Nov 07, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.4

(source)

DANN

Benign

0.88

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.27

.;.;.;T;T

MetaRNN

Benign

0.000018

T;T;T;T;T

MetaSVM

Benign

-0.91

PhyloP100

-0.46

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.37

T;T;T;T;T

Sift4G

Benign

0.093

T;T;T;T;T

Polyphen

0.26, 0.99

.;.;.;B;D

Vest4

0.082

MPC

0.30

ClinPred

0.022

GERP RS

-2.0

gMVP

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over