Variant 1-207506725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000651.6(CR1):c.313C>T(p.Arg105Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,613,150 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 86 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064602196).

BP6

Variant 1-207506725-C-T is Benign according to our data. Variant chr1-207506725-C-T is described in ClinVar as [Benign]. Clinvar id is 3024765.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.313C>T	p.Arg105Cys	missense_variant	Exon 3 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.313C>T	p.Arg105Cys	missense_variant	Exon 3 of 47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1123

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00738

AC:

1836

AN:

248936

Hom.:

AF XY:

0.00746

AC XY:

1008

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.00686

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00745

GnomAD4 exome

AF:

0.00919

AC:

13432

AN:

1460892

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

6470

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.00334

Gnomad4 ASJ exome

AF:

0.00544

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00288

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.00738

AC:

1123

AN:

152258

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.00622

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0103

AC:

ExAC

AF:

0.00759

AC:

917

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.00937

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CR1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.72

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.33

.;.;.;T;T

MetaRNN

Benign

0.0065

T;T;T;T;T

MetaSVM

Benign

-0.67

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.043

D;D;D;D;T

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.99, 1.0

.;.;.;D;D

Vest4

0.20

MVP

0.62

MPC

0.45

ClinPred

0.046

GERP RS

-7.7

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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