NM_000651.6:c.487+5872G>C

Variant names:

• chr1-207517526-G-C
• rs10863358
• NM_000651.6:c.487+5872G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000651.6(CR1):​c.487+5872G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,890 control chromosomes in the GnomAD database, including 5,236 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 0.26 (5236 hom., cov: 32)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.54
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000651.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.487+5872G>C		intron	N/A	NP_000642.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.487+5872G>C		intron	N/A	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.487+5872G>C		intron	N/A	ENSP00000383744.2
	CR1	ENST00000367050.8	TSL:1	n.608+5872G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38951 AN: 151772 Hom.: 5226 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 38992 AN: 151890 Hom.: 5236 Cov.: 32 AF XY: 0.263 AC XY: 19493 AN XY: 74252

African (AFR) AF: 0.287 AC: 11900 AN: 41414

American (AMR) AF: 0.298 AC: 4551 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1038 AN: 3464

East Asian (EAS) AF: 0.288 AC: 1491 AN: 5176

South Asian (SAS) AF: 0.445 AC: 2139 AN: 4810

European-Finnish (FIN) AF: 0.238 AC: 2508 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14523 AN: 67896

Other (OTH) AF: 0.252 AC: 529 AN: 2100

Alfa AF: 0.234 Hom.: 599

Bravo AF: 0.258

Asia WGS AF: 0.446 AC: 1545 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0010
DANN	Benign	0.41
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10863358; hg19: chr1-207690871;