1-207563993-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000651.6(CR1):c.3716G>A(p.Arg1239His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 1,522,900 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00077 ( 5 hom., cov: 18)

Exomes 𝑓: 0.00090 ( 150 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.291

Publications

3 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:

CR1-AS1 (HGNC:40160):

CR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0656406).

BS2

High Homozygotes in GnomAd4 at 5 BG gene

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.3716G>A	p.Arg1239His	missense	Exon 22 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.3716G>A	p.Arg1239His	missense	Exon 22 of 47	ENSP00000356016.4	E9PDY4
CR1	ENST00000400960.7	TSL:1	c.2366G>A	p.Arg789His	missense	Exon 14 of 39	ENSP00000383744.2	P17927
CR1	ENST00000367051.6	TSL:5	c.2366G>A	p.Arg789His	missense	Exon 14 of 39	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

AN:

120936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.000562

GnomAD2 exomes

AF:

0.000534

AC:

122

AN:

228592

AF XY:

0.000564

show subpopulations

Gnomad AFR exome

AF:

0.000214

Gnomad AMR exome

AF:

0.000286

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000584

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000984

Gnomad OTH exome

AF:

0.000521

GnomAD4 exome

AF:

0.000901

AC:

1263

AN:

1401914

Hom.:

150

Cov.:

AF XY:

0.000842

AC XY:

588

AN XY:

698056

show subpopulations

African (AFR)

AF:

0.000683

AC:

AN:

19030

American (AMR)

AF:

0.000437

AC:

AN:

41202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24836

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38794

South Asian (SAS)

AF:

0.00

AC:

AN:

78328

European-Finnish (FIN)

AF:

0.0000381

AC:

AN:

52458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5158

European-Non Finnish (NFE)

AF:

0.00110

AC:

1191

AN:

1084672

Other (OTH)

AF:

0.000662

AC:

AN:

57436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.000769

AC:

AN:

120986

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

58732

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

18428

American (AMR)

AF:

0.00145

AC:

AN:

13064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3190

East Asian (EAS)

AF:

0.00

AC:

AN:

4694

South Asian (SAS)

AF:

0.00

AC:

AN:

3676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00105

AC:

AN:

65064

Other (OTH)

AF:

0.000558

AC:

AN:

1792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000476

Hom.:

ESP6500AA

AF:

0.000377

AC:

ESP6500EA

AF:

0.00111

AC:

ExAC

AF:

0.000480

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.5

(source)

DANN

Benign

0.81

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.14

M_CAP

Benign

0.018

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

PhyloP100

-0.29

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.54

REVEL

Benign

0.043

Sift

Benign

0.34

Sift4G

Benign

0.67

Polyphen

0.53

Vest4

0.063

MVP

0.35

MPC

2.1

ClinPred

0.0018

GERP RS

-2.7

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(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