Variant rs3737002 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000651.6(CR1):c.5573C>T(p.Thr1858Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,346 control chromosomes in the GnomAD database, including 64,072 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1858A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.23 ( 4928 hom., cov: 33)

Exomes 𝑓: 0.28 ( 59144 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.587

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00201419).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR1	NM_000651.6 linkuse as main transcript	c.5573C>T	p.Thr1858Met	missense_variant	34/47	ENST00000367049.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR1	ENST00000367049.9 linkuse as main transcript	c.5573C>T	p.Thr1858Met	missense_variant	34/47	5	NM_000651.6	P1
	ENST00000597497.5 linkuse as main transcript	n.352+11418G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34978

AN:

152024

Hom.:

4922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0754

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.241

GnomAD3 exomes

AF:

0.282

AC:

70327

AN:

248984

Hom.:

10548

AF XY:

0.283

AC XY:

38225

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.280

AC:

409370

AN:

1461204

Hom.:

59144

Cov.:

AF XY:

0.281

AC XY:

204001

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.230

AC:

34990

AN:

152142

Hom.:

4928

Cov.:

AF XY:

0.237

AC XY:

17614

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0754

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.261

Hom.:

10039

Bravo

AF:

0.224

TwinsUK

AF:

0.293

AC:

1087

ALSPAC

AF:

0.281

AC:

1082

ESP6500AA

AF:

0.0748

AC:

272

ESP6500EA

AF:

0.276

AC:

2253

ExAC

AF:

0.275

AC:

33182

Asia WGS

AF:

0.262

AC:

912

AN:

3478

EpiCase

AF:

0.267

EpiControl

AF:

0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.2

DANN

Uncertain

0.99

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.40

.;.;.;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.85

N;N;N;N;N

REVEL

Benign

0.092

Sift

Uncertain

0.019

D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.99, 1.0

.;.;.;D;D

Vest4

0.13

MPC

0.52

ClinPred

0.012

GERP RS

-0.082

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over