rs56170518

Variant names:

• chr1-207563931-C-T
• rs56170518
• NM_000651.6:c.3654C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-207563931-C-T
• chr1-207563931-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000651.6(CR1):​c.3654C>T​(p.Pro1218Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,479,902 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 16)
  • Exomes 𝑓: 0.0097 (1140 hom.)
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-207563931-C-T is Benign according to our data. Variant chr1-207563931-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0141 (1593/113012) while in subpopulation NFE AF = 0.0186 (1179/63234). AF 95% confidence interval is 0.0178. There are 44 homozygotes in GnomAd4. There are 696 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 BG gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.3654C>T	p.Pro1218Pro	synonymous	Exon 22 of 47	NP_000642.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.3654C>T	p.Pro1218Pro	synonymous	Exon 22 of 47	ENSP00000356016.4	E9PDY4
	CR1	ENST00000400960.7	TSL:1	c.2304C>T	p.Pro768Pro	synonymous	Exon 14 of 39	ENSP00000383744.2	P17927
	CR1	ENST00000367051.6	TSL:5	c.2304C>T	p.Pro768Pro	synonymous	Exon 14 of 39	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 1593 AN: 112978 Hom.: 44 Cov.: 16

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.0293

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00958

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.00727

GnomAD2 exomes AF: 0.00222 AC: 500 AN: 225682 AF XY: 0.00228

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.000871

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000630

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.00351

GnomAD4 exome AF: 0.00972 AC: 13280 AN: 1366890 Hom.: 1140 Cov.: 31 AF XY: 0.00989 AC XY: 6738 AN XY: 681050

African (AFR) AF: 0.00353 AC: 62 AN: 17584

American (AMR) AF: 0.00615 AC: 250 AN: 40632

Ashkenazi Jewish (ASJ) AF: 0.00633 AC: 155 AN: 24478

East Asian (EAS) AF: 0.000130 AC: 5 AN: 38434

South Asian (SAS) AF: 0.0117 AC: 898 AN: 76574

European-Finnish (FIN) AF: 0.0164 AC: 846 AN: 51580

Middle Eastern (MID) AF: 0.00825 AC: 39 AN: 4730

European-Non Finnish (NFE) AF: 0.00987 AC: 10425 AN: 1056690

Other (OTH) AF: 0.0107 AC: 600 AN: 56188

GnomAD4 genome AF: 0.0141 AC: 1593 AN: 113012 Hom.: 44 Cov.: 16 AF XY: 0.0127 AC XY: 696 AN XY: 54762

African (AFR) AF: 0.00421 AC: 62 AN: 14720

American (AMR) AF: 0.0107 AC: 130 AN: 12150

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 32 AN: 3074

East Asian (EAS) AF: 0.00 AC: 0 AN: 4468

South Asian (SAS) AF: 0.00958 AC: 31 AN: 3236

European-Finnish (FIN) AF: 0.0130 AC: 122 AN: 9386

Middle Eastern (MID) AF: 0.00373 AC: 1 AN: 268

European-Non Finnish (NFE) AF: 0.0186 AC: 1179 AN: 63234

Other (OTH) AF: 0.00725 AC: 12 AN: 1656

Alfa AF: 0.0177 Hom.: 17

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs56170518; hg19: chr1-207737276;