Variant 1-207505962-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000651.6(CR1):c.180A>G(p.Glu60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,613,790 control chromosomes in the GnomAD database, including 537,734 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 54246 hom., cov: 32)

Exomes 𝑓: 0.81 ( 483488 hom. )

Consequence

CR1
NM_000651.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP7

Synonymous conserved (PhyloP=-1.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1	NM_000651.6 linkuse as main transcript	c.180A>G	p.Glu60=	synonymous_variant	2/47	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 linkuse as main transcript	c.180A>G	p.Glu60=	synonymous_variant	2/47	5	NM_000651.6	ENSP00000356016	P1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127818

AN:

152092

Hom.:

54186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.936

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.799

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.840

GnomAD3 exomes

AF:

0.822

AC:

204844

AN:

249130

Hom.:

85021

AF XY:

0.820

AC XY:

110870

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.941

Gnomad AMR exome

AF:

0.905

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.631

Gnomad SAS exome

AF:

0.891

Gnomad FIN exome

AF:

0.795

Gnomad NFE exome

AF:

0.800

Gnomad OTH exome

AF:

0.807

GnomAD4 exome

AF:

0.812

AC:

1186500

AN:

1461580

Hom.:

483488

Cov.:

AF XY:

0.813

AC XY:

591100

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.944

Gnomad4 AMR exome

AF:

0.901

Gnomad4 ASJ exome

AF:

0.800

Gnomad4 EAS exome

AF:

0.617

Gnomad4 SAS exome

AF:

0.886

Gnomad4 FIN exome

AF:

0.797

Gnomad4 NFE exome

AF:

0.806

Gnomad4 OTH exome

AF:

0.809

GnomAD4 genome

AF:

0.841

AC:

127936

AN:

152210

Hom.:

54246

Cov.:

AF XY:

0.840

AC XY:

62522

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.936

Gnomad4 AMR

AF:

0.857

Gnomad4 ASJ

AF:

0.799

Gnomad4 EAS

AF:

0.629

Gnomad4 SAS

AF:

0.892

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.801

Gnomad4 OTH

AF:

0.840

Alfa

AF:

0.802

Hom.:

7060

Bravo

AF:

0.848

Asia WGS

AF:

0.804

AC:

2795

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.47

DANN

Benign

0.49

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