rs677066

Positions:

• chr1-207600646-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000651.6(CR1):​c.5811-6605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,060 control chromosomes in the GnomAD database, including 16,556 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 0.40 (16556 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1	NM_000651.6	c.5811-6605T>C		intron_variant		ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.5811-6605T>C		intron_variant		5	NM_000651.6	ENSP00000356016	P1
	ENST00000597497.5	n.192-1640A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60570 AN: 151940 Hom.: 16519 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.399 AC: 60663 AN: 152058 Hom.: 16556 Cov.: 32 AF XY: 0.400 AC XY: 29743 AN XY: 74344

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.359

Alfa AF: 0.285 Hom.: 4136

Bravo AF: 0.420

Asia WGS AF: 0.484 AC: 1678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.61

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: rs677066; hg19: chr1-207773991;