1-207505962-A-G

Variant names:

• chr1-207505962-A-G
• rs4844600
• NM_000651.6:c.180A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000651.6(CR1):​c.180A>G​(p.Glu60Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,613,790 control chromosomes in the GnomAD database, including 537,734 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 0.84 (54246 hom., cov: 32)
  • Exomes 𝑓: 0.81 (483488 hom.)
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 34 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.046).
• BP7: Synonymous conserved (PhyloP=-1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 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.180A>G	p.Glu60Glu	synonymous	Exon 2 of 47	NP_000642.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.180A>G	p.Glu60Glu	synonymous	Exon 2 of 47	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.180A>G	p.Glu60Glu	synonymous	Exon 2 of 39	ENSP00000383744.2
	CR1	ENST00000367050.8	TSL:1	n.301A>G		non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127818 AN: 152092 Hom.: 54186 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.840

GnomAD2 exomes AF: 0.822 AC: 204844 AN: 249130 AF XY: 0.820

Gnomad AFR exome AF: 0.941

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.800

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.795

Gnomad NFE exome AF: 0.800

Gnomad OTH exome AF: 0.807

GnomAD4 exome AF: 0.812 AC: 1186500 AN: 1461580 Hom.: 483488 Cov.: 59 AF XY: 0.813 AC XY: 591100 AN XY: 727092

African (AFR) AF: 0.944 AC: 31581 AN: 33472

American (AMR) AF: 0.901 AC: 40279 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 20915 AN: 26130

East Asian (EAS) AF: 0.617 AC: 24499 AN: 39694

South Asian (SAS) AF: 0.886 AC: 76395 AN: 86250

European-Finnish (FIN) AF: 0.797 AC: 42559 AN: 53402

Middle Eastern (MID) AF: 0.830 AC: 4788 AN: 5766

European-Non Finnish (NFE) AF: 0.806 AC: 896616 AN: 1111788

Other (OTH) AF: 0.809 AC: 48868 AN: 60370

GnomAD4 genome AF: 0.841 AC: 127936 AN: 152210 Hom.: 54246 Cov.: 32 AF XY: 0.840 AC XY: 62522 AN XY: 74402

African (AFR) AF: 0.936 AC: 38915 AN: 41564

American (AMR) AF: 0.857 AC: 13109 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2775 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3258 AN: 5180

South Asian (SAS) AF: 0.892 AC: 4299 AN: 4818

European-Finnish (FIN) AF: 0.795 AC: 8403 AN: 10576

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54453 AN: 67982

Other (OTH) AF: 0.840 AC: 1771 AN: 2108

Alfa AF: 0.496 Hom.: 7060

Bravo AF: 0.848

Asia WGS AF: 0.804 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.49
PhyloP100		-1.5
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: rs4844600; hg19: chr1-207679307; COSMIC: COSV100888135;