rs17047660

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.6118A>G(p.Lys2040Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,613,850 control chromosomes in the GnomAD database, including 2,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.068 ( 1158 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 1050 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.526

Publications

57 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=0.017027318).

BP6

Variant 1-207609511-A-G is Benign according to our data. Variant chr1-207609511-A-G is described in ClinVar as Benign. ClinVar VariationId is 3056450.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.6118A>G	p.Lys2040Glu	missense_variant	Exon 37 of 47	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 link	c.6118A>G	p.Lys2040Glu	missense_variant	Exon 37 of 47	5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10257

AN:

152094

Hom.:

1153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0526

GnomAD2 exomes

AF:

0.0182

AC:

4520

AN:

248948

AF XY:

0.0136

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00877

GnomAD4 exome

AF:

0.00756

AC:

11057

AN:

1461638

Hom.:

1050

Cov.:

AF XY:

0.00662

AC XY:

4816

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.244

AC:

8163

AN:

33456

American (AMR)

AF:

0.0137

AC:

613

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00949

AC:

248

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000533

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000742

AC:

825

AN:

1111848

Other (OTH)

AF:

0.0177

AC:

1068

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

461

923

1384

1846

2307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.0676

AC:

10282

AN:

152212

Hom.:

1158

Cov.:

AF XY:

0.0655

AC XY:

4875

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.231

AC:

9595

AN:

41490

American (AMR)

AF:

0.0289

AC:

442

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

68014

Other (OTH)

AF:

0.0521

AC:

110

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

411

822

1234

1645

2056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0251

Hom.:

1405

Bravo

AF:

0.0772

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.220

AC:

832

ESP6500EA

AF:

0.00182

AC:

ExAC

AF:

0.0214

AC:

2579

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CR1-related disorder

Benign:1

Nov 26, 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

0.20

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.54

.;.;.;T;T

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

0.53

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.085

Sift

Benign

0.065

T;T;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.0050, 0.96

.;.;.;B;D

Vest4

0.053

MPC

0.31

ClinPred

0.0044

GERP RS

1.4

gMVP

0.47

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