Variant 1-207609571-A-T 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.6178A>T(p.Thr2060Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,613,696 control chromosomes in the GnomAD database, including 774,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.99 ( 73972 hom., cov: 31)

Exomes 𝑓: 0.98 ( 700790 hom. )

Consequence

CR1
NM_000651.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.871

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=1.904434E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.6178A>T	p.Thr2060Ser	missense_variant	37/47	ENST00000367049.9	NP_000642.3	P17927E9PDY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 link	c.6178A>T	p.Thr2060Ser	missense_variant	37/47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

149966

AN:

152168

Hom.:

73913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.995

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.975

Gnomad OTH

AF:

0.993

GnomAD3 exomes

AF:

0.985

AC:

244723

AN:

248328

Hom.:

120608

AF XY:

0.986

AC XY:

132813

AN XY:

134748

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.990

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.996

Gnomad FIN exome

AF:

0.986

Gnomad NFE exome

AF:

0.976

Gnomad OTH exome

AF:

0.987

GnomAD4 exome

AF:

0.979

AC:

1431126

AN:

1461410

Hom.:

700790

Cov.:

AF XY:

0.980

AC XY:

712096

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.997

Gnomad4 AMR exome

AF:

0.992

Gnomad4 ASJ exome

AF:

0.990

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

0.985

Gnomad4 NFE exome

AF:

0.975

Gnomad4 OTH exome

AF:

0.985

GnomAD4 genome

AF:

0.986

AC:

150084

AN:

152286

Hom.:

73972

Cov.:

AF XY:

0.987

AC XY:

73463

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.995

Gnomad4 AMR

AF:

0.992

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.998

Gnomad4 FIN

AF:

0.989

Gnomad4 NFE

AF:

0.975

Gnomad4 OTH

AF:

0.993

Alfa

AF:

0.978

Hom.:

54957

Bravo

AF:

0.986

TwinsUK

AF:

0.973

AC:

3607

ALSPAC

AF:

0.980

AC:

3775

ESP6500AA

AF:

0.996

AC:

3818

ESP6500EA

AF:

0.975

AC:

8041

ExAC

AF:

0.985

AC:

119016

Asia WGS

AF:

0.998

AC:

3471

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.23

DANN

Benign

0.13

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.16

.;.;.;T;T

MetaRNN

Benign

0.0000019

T;T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.34

PROVEAN

Benign

0.76

N;N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.80

T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.0, 0.0030

.;.;.;B;B

Vest4

0.019

MutPred

0.54

.;.;.;.;Loss of stability (P = 0.1743);

MPC

0.099

ClinPred

0.0016

GERP RS

2.5

gMVP

0.22

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