1-207609586-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000651.6(CR1):c.6193A>G(p.Ile2065Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,612,446 control chromosomes in the GnomAD database, including 69,496 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I2065F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.40 ( 16803 hom., cov: 31)

Exomes 𝑓: 0.24 ( 52693 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

Publications

77 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.2969766E-6).

BP6

Variant 1-207609586-A-G is Benign according to our data. Variant chr1-207609586-A-G is described in ClinVar as Benign. ClinVar VariationId is 1252113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000651.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.6193A>G	p.Ile2065Val	missense	Exon 37 of 47	NP_000642.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CR1	ENST00000367049.9	TSL:5 MANE Select	c.6193A>G	p.Ile2065Val	missense	Exon 37 of 47	ENSP00000356016.4	E9PDY4
CR1	ENST00000400960.7	TSL:1	c.4843A>G	p.Ile1615Val	missense	Exon 29 of 39	ENSP00000383744.2	P17927
CR1	ENST00000367051.6	TSL:5	c.4843A>G	p.Ile1615Val	missense	Exon 29 of 39	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60820

AN:

151966

Hom.:

16765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.352

GnomAD2 exomes

AF:

0.321

AC:

79225

AN:

246530

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.797

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.243

AC:

355524

AN:

1460362

Hom.:

52693

Cov.:

AF XY:

0.248

AC XY:

179804

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.803

AC:

26869

AN:

33454

American (AMR)

AF:

0.402

AC:

17877

AN:

44450

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8384

AN:

26086

East Asian (EAS)

AF:

0.267

AC:

10585

AN:

39660

South Asian (SAS)

AF:

0.428

AC:

36850

AN:

86102

European-Finnish (FIN)

AF:

0.244

AC:

13009

AN:

53332

Middle Eastern (MID)

AF:

0.310

AC:

1790

AN:

5768

European-Non Finnish (NFE)

AF:

0.201

AC:

223183

AN:

1111166

Other (OTH)

AF:

0.281

AC:

16977

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13641

27282

40923

54564

68205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8132

16264

24396

32528

40660

<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:

0.401

AC:

60914

AN:

152084

Hom.:

16803

Cov.:

AF XY:

0.402

AC XY:

29871

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.783

AC:

32446

AN:

41456

American (AMR)

AF:

0.362

AC:

5536

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1103

AN:

3472

East Asian (EAS)

AF:

0.306

AC:

1582

AN:

5176

South Asian (SAS)

AF:

0.445

AC:

2142

AN:

4814

European-Finnish (FIN)

AF:

0.241

AC:

2557

AN:

10596

Middle Eastern (MID)

AF:

0.267

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.213

AC:

14471

AN:

67980

Other (OTH)

AF:

0.358

AC:

754

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1420

2840

4261

5681

7101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.286

Hom.:

32181

Bravo

AF:

0.422

TwinsUK

AF:

0.199

AC:

737

ALSPAC

AF:

0.186

AC:

716

ESP6500AA

AF:

0.751

AC:

2892

ESP6500EA

AF:

0.213

AC:

1761

ExAC

AF:

0.327

AC:

39530

Asia WGS

AF:

0.483

AC:

1677

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.1

(source)

DANN

Benign

0.11

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0000063

MetaSVM

Benign

-0.96

PhyloP100

2.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.60

REVEL

Benign

0.090

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0090

MPC

0.092

ClinPred

0.0012

GERP RS

2.5

gMVP

0.17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over