rs6691117

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.6193A>G	p.Ile2065Val	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.6193A>G	p.Ile2065Val	missense_variant	Exon 37 of 47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

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

GnomAD3 exomes

AF:

0.321

AC:

79225

AN:

246530

Hom.:

15674

AF XY:

0.315

AC XY:

42110

AN XY:

133756

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 SAS exome

AF:

0.432

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

Gnomad4 AFR exome

AF:

0.803

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.267

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.401

AC:

60914

AN:

152084

Hom.:

16803

Cov.:

AF XY:

0.402

AC XY:

29871

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.783

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.256

Hom.:

15212

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23856853, 31182772, 21700265, 24018213, 23591632) -

CR1-related disorder

Benign:1

Oct 17, 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

0.060

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.1

DANN

Benign

0.11

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.37

.;.;.;T;T

MetaRNN

Benign

0.0000063

T;T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.60

N;N;N;N;N

REVEL

Benign

0.090

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0, 0.0010

.;.;.;B;B

Vest4

0.0090

MPC

0.092

ClinPred

0.0012

GERP RS

2.5

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over