Genetic Variant CR1:p.Val1868Val (chr1-207587459-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B.

-11

BP4_StrongBP6_ModerateBP7BS2

The NM_000651.6(CR1):c.5604C>T(p.Val1868Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 1,613,872 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 8 hom., cov: 33)

Exomes 𝑓: 0.010 ( 102 hom. )

Consequence

CR1
NM_000651.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.302

Publications

9 publications found

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:

CR1-AS1 (HGNC:40160):

CR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-207587459-C-T is Benign according to our data. Variant chr1-207587459-C-T is described in ClinVar as [Benign]. Clinvar id is 2639874.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.302 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.5604C>T	p.Val1868Val	synonymous_variant	Exon 34 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.5604C>T	p.Val1868Val	synonymous_variant	Exon 34 of 47	5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00798

AC:

1987

AN:

249142

AF XY:

0.00798

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00811

GnomAD4 exome

AF:

0.0101

AC:

14812

AN:

1461562

Hom.:

102

Cov.:

AF XY:

0.00996

AC XY:

7244

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33478

American (AMR)

AF:

0.00293

AC:

131

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

420

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.00195

AC:

168

AN:

86240

European-Finnish (FIN)

AF:

0.0193

AC:

1030

AN:

53402

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0112

AC:

12434

AN:

1111752

Other (OTH)

AF:

0.00929

AC:

561

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

721

1441

2162

2882

3603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

478

956

1434

1912

2390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00822

AC:

1252

AN:

152310

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

663

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41576

American (AMR)

AF:

0.00431

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00249

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0264

AC:

280

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

721

AN:

68028

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CR1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.72

(source)

DANN

Benign

0.53

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over