rs12144461

chr1-207587459-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000651.6(CR1):c.5604C>T(p.Val1868=) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (8 hom., cov: 33)
  • Exomes 𝑓: 0.010 (102 hom.)
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_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 GnomAd at 8 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR1	NM_000651.6	c.5604C>T	p.Val1868=	synonymous_variant	34/47	ENST00000367049.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR1	ENST00000367049.9	c.5604C>T	p.Val1868=	synonymous_variant	34/47	5	NM_000651.6	P1
	ENST00000597497.5	n.352+11387G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1252 AN: 152192 Hom.: 8 Cov.: 33

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

GnomAD3 exomes AF: 0.00798 AC: 1987 AN: 249142 Hom.: 14 AF XY: 0.00798 AC XY: 1078 AN XY: 135166

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 SAS exome AF: 0.00203

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.: 31 AF XY: 0.00996 AC XY: 7244 AN XY: 727074

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00929

GnomAD4 genome AF: 0.00822 AC: 1252 AN: 152310 Hom.: 8 Cov.: 33 AF XY: 0.00890 AC XY: 663 AN XY: 74476

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0106 Hom.: 3

Bravo AF: 0.00660

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.0109

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

CR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.72
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs12144461; hg19: chr1-207760804;