Variant chr1-207621975-A-G 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.7255A>G(p.Thr2419Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,593,392 control chromosomes in the GnomAD database, including 532,780 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 50485 hom., cov: 31)

Exomes 𝑓: 0.82 ( 482295 hom. )

Consequence

CR1
NM_000651.6 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.00

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:

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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=1.6148501E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.7255A>G	p.Thr2419Ala	missense_variant, splice_region_variant	44/47	ENST00000367049.9	NP_000642.3	P17927E9PDY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 link	c.7255A>G	p.Thr2419Ala	missense_variant, splice_region_variant	44/47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.813

AC:

123577

AN:

151992

Hom.:

50449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.860

Gnomad ASJ

AF:

0.811

Gnomad EAS

AF:

0.658

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.834

GnomAD3 exomes

AF:

0.819

AC:

187609

AN:

228938

Hom.:

77449

AF XY:

0.820

AC XY:

101209

AN XY:

123444

show subpopulations

Gnomad AFR exome

AF:

0.807

Gnomad AMR exome

AF:

0.907

Gnomad ASJ exome

AF:

0.811

Gnomad EAS exome

AF:

0.654

Gnomad SAS exome

AF:

0.902

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.816

GnomAD4 exome

AF:

0.817

AC:

1177041

AN:

1441282

Hom.:

482295

Cov.:

AF XY:

0.818

AC XY:

585561

AN XY:

715600

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.902

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.638

Gnomad4 SAS exome

AF:

0.898

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.814

Gnomad4 OTH exome

AF:

0.815

GnomAD4 genome

AF:

0.813

AC:

123666

AN:

152110

Hom.:

50485

Cov.:

AF XY:

0.815

AC XY:

60604

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.814

Gnomad4 AMR

AF:

0.860

Gnomad4 ASJ

AF:

0.811

Gnomad4 EAS

AF:

0.657

Gnomad4 SAS

AF:

0.902

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.807

Gnomad4 OTH

AF:

0.834

Alfa

AF:

0.804

Hom.:

25911

Bravo

AF:

0.815

TwinsUK

AF:

0.818

AC:

3034

ALSPAC

AF:

0.821

AC:

3164

ESP6500AA

AF:

0.817

AC:

3108

ESP6500EA

AF:

0.817

AC:

6750

ExAC

AF:

0.808

AC:

97310

Asia WGS

AF:

0.807

AC:

2806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0040

DANN

Benign

0.16

Eigen

Benign

-2.9

Eigen_PC

Benign

-3.0

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.19

.;.;.;T;T

MetaRNN

Benign

0.0000016

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.0

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.99

T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.0

.;.;.;.;B

Vest4

0.020

MPC

0.11

ClinPred

0.0025

GERP RS

-8.3

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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