1-207565782-A-G

Variant names:

• chr1-207565782-A-G
• rs3886100
• NM_000651.6:c.3867-56A>G

Variant summary

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

The NM_000651.6(CR1):​c.3867-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 149,706 control chromosomes in the GnomAD database, including 19,230 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 0.46 (19230 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250880 hom.)
  • Failed GnomAD Quality Control
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 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.3867-56A>G		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.3867-56A>G		intron	N/A	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.2517-56A>G		intron	N/A	ENSP00000383744.2
	CR1	ENST00000367051.6	TSL:5	c.2517-56A>G		intron	N/A	ENSP00000356018.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 69474 AN: 149590 Hom.: 19222 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.517

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.577 AC: 839157 AN: 1454976 Hom.: 250880 AF XY: 0.573 AC XY: 415114 AN XY: 724238

African (AFR) AF: 0.196 AC: 6224 AN: 31826

American (AMR) AF: 0.522 AC: 23232 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12716 AN: 26094

East Asian (EAS) AF: 0.375 AC: 14850 AN: 39616

South Asian (SAS) AF: 0.459 AC: 39487 AN: 86108

European-Finnish (FIN) AF: 0.556 AC: 29657 AN: 53316

Middle Eastern (MID) AF: 0.537 AC: 3037 AN: 5654

European-Non Finnish (NFE) AF: 0.611 AC: 677288 AN: 1107806

Other (OTH) AF: 0.544 AC: 32666 AN: 60032

GnomAD4 genome AF: 0.464 AC: 69492 AN: 149706 Hom.: 19230 Cov.: 32 AF XY: 0.463 AC XY: 33865 AN XY: 73190

African (AFR) AF: 0.207 AC: 8157 AN: 39378

American (AMR) AF: 0.522 AC: 7940 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1849 AN: 5170

South Asian (SAS) AF: 0.450 AC: 2158 AN: 4800

European-Finnish (FIN) AF: 0.552 AC: 5823 AN: 10546

Middle Eastern (MID) AF: 0.566 AC: 164 AN: 290

European-Non Finnish (NFE) AF: 0.592 AC: 40168 AN: 67864

Other (OTH) AF: 0.510 AC: 1062 AN: 2082

Alfa AF: 0.504 Hom.: 2691

Bravo AF: 0.452

Asia WGS AF: 0.336 AC: 1168 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		-0.23
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: rs3886100; hg19: chr1-207739127; COSMIC: COSV65465444; COSMIC: COSV65465444;