rs9429782

Variant names:

• chr1-207496010-G-T
• rs9429782
• NM_000651.6:c.-258G>T

Variant summary

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

The NM_000651.6(CR1):​c.-258G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 506,914 control chromosomes in the GnomAD database, including 1,047 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 0.027 (277 hom., cov: 32)
  • Exomes 𝑓: 0.032 (770 hom.)
• Consequence: CR1 NM_000651.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6	c.-258G>T		upstream_gene_variant		ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.-258G>T		upstream_gene_variant		5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4127 AN: 152178 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00794

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0316 AC: 11190 AN: 354618 Hom.: 770 AF XY: 0.0349 AC XY: 6542 AN XY: 187488

Gnomad4 AFR exome AF: 0.0260

Gnomad4 AMR exome AF: 0.00561

Gnomad4 ASJ exome AF: 0.0311

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.0829

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.00833

Gnomad4 OTH exome AF: 0.0333

GnomAD4 genome AF: 0.0270 AC: 4116 AN: 152296 Hom.: 277 Cov.: 32 AF XY: 0.0301 AC XY: 2242 AN XY: 74468

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0233

Gnomad4 NFE AF: 0.00794

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0133 Hom.: 8

Bravo AF: 0.0262

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9429782; hg19: chr1-207669355;