rs561614144

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_000651.6(CR1):c.3731G>A(p.Gly1244Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000321 in 1,403,728 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 18)

Exomes 𝑓: 0.000032 ( 10 hom. )

Failed GnomAD Quality Control

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Publications

2 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30091244).

BS2

High Homozygotes in GnomAdExome4 at 10 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.3731G>A	p.Gly1244Glu	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.3731G>A	p.Gly1244Glu	missense	Exon 22 of 47	ENSP00000356016.4	E9PDY4
CR1	ENST00000400960.7	TSL:1	c.2381G>A	p.Gly794Glu	missense	Exon 14 of 39	ENSP00000383744.2	P17927
CR1	ENST00000367051.6	TSL:5	c.2381G>A	p.Gly794Glu	missense	Exon 14 of 39	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

121568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000461

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000110

AC:

AN:

227638

AF XY:

0.0000807

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.000159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000741

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000321

AC:

AN:

1403728

Hom.:

Cov.:

AF XY:

0.0000258

AC XY:

AN XY:

698932

show subpopulations

African (AFR)

AF:

0.000820

AC:

AN:

19522

American (AMR)

AF:

0.000145

AC:

AN:

41336

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24904

East Asian (EAS)

AF:

0.00

AC:

AN:

38826

South Asian (SAS)

AF:

0.00

AC:

AN:

78548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52498

Middle Eastern (MID)

AF:

0.000392

AC:

AN:

5106

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

1085454

Other (OTH)

AF:

0.0000521

AC:

AN:

57534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000123

AC:

AN:

121618

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

58996

show subpopulations

African (AFR)

AF:

0.000632

AC:

AN:

18976

American (AMR)

AF:

0.00

AC:

AN:

13082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3204

East Asian (EAS)

AF:

0.00

AC:

AN:

4702

South Asian (SAS)

AF:

0.00

AC:

AN:

3684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000461

AC:

AN:

65114

Other (OTH)

AF:

0.00

AC:

AN:

1780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.698

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000877

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

Uncertain

0.48

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.054

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.36

PhyloP100

2.1

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.54

Sift

Uncertain

0.023

Sift4G

Uncertain

0.0060

Polyphen

0.98

Vest4

0.33

MutPred

0.86

Gain of catalytic residue at W1246 (P = 0.0685)

MVP

0.81

MPC

3.7

ClinPred

0.14

GERP RS

3.1

gMVP

0.82

Mutation Taster

=98/2

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