rs646817

Variant names:

• chr1-207584591-A-G
• rs646817
• NM_000651.6:c.5303-58A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-207584591-A-G
• chr1-207584591-A-T

Variant summary

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

The NM_000651.6(CR1):​c.5303-58A>G 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 1,565,870 control chromosomes in the GnomAD database, including 66,423 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 (16425 hom., cov: 32)
  • Exomes 𝑓: 0.24 (49998 hom.)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 18 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]

CR1-AS1 (HGNC:40160):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6	c.5303-58A>G		intron_variant	Intron 32 of 46	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.5303-58A>G		intron_variant	Intron 32 of 46	5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60207 AN: 151974 Hom.: 16389 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.242 AC: 341775 AN: 1413778 Hom.: 49998 AF XY: 0.246 AC XY: 172424 AN XY: 701354

African (AFR) AF: 0.793 AC: 25499 AN: 32150

American (AMR) AF: 0.393 AC: 16211 AN: 41256

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 7612 AN: 23724

East Asian (EAS) AF: 0.252 AC: 9899 AN: 39334

South Asian (SAS) AF: 0.428 AC: 34369 AN: 80218

European-Finnish (FIN) AF: 0.236 AC: 12249 AN: 51830

Middle Eastern (MID) AF: 0.311 AC: 1718 AN: 5532

European-Non Finnish (NFE) AF: 0.201 AC: 217856 AN: 1081326

Other (OTH) AF: 0.280 AC: 16362 AN: 58408

GnomAD4 genome AF: 0.396 AC: 60296 AN: 152092 Hom.: 16425 Cov.: 32 AF XY: 0.397 AC XY: 29533 AN XY: 74324

African (AFR) AF: 0.773 AC: 32061 AN: 41484

American (AMR) AF: 0.357 AC: 5452 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1488 AN: 5178

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4816

European-Finnish (FIN) AF: 0.234 AC: 2474 AN: 10580

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14490 AN: 67970

Other (OTH) AF: 0.358 AC: 757 AN: 2116

Alfa AF: 0.296 Hom.: 14824

Bravo AF: 0.418

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.36
PhyloP100		-0.14
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: rs646817; hg19: chr1-207757936;