1-207584170-A-G

Variant names:

• chr1-207584170-A-G
• rs12034598
• NM_000651.6:c.5303-479A>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.5303-479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,098 control chromosomes in the GnomAD database, including 3,070 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 0.19 (3070 hom., cov: 32)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 21 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=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 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.5303-479A>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.5303-479A>G		intron	N/A	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.3953-479A>G		intron	N/A	ENSP00000383744.2
	CR1	ENST00000367051.6	TSL:5	c.3953-479A>G		intron	N/A	ENSP00000356018.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29016 AN: 151980 Hom.: 3070 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.191 AC: 29021 AN: 152098 Hom.: 3070 Cov.: 32 AF XY: 0.197 AC XY: 14625 AN XY: 74364

African (AFR) AF: 0.135 AC: 5608 AN: 41520

American (AMR) AF: 0.257 AC: 3930 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1482 AN: 5174

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4822

European-Finnish (FIN) AF: 0.180 AC: 1905 AN: 10560

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12300 AN: 67962

Other (OTH) AF: 0.199 AC: 420 AN: 2108

Alfa AF: 0.189 Hom.: 8036

Bravo AF: 0.188

Asia WGS AF: 0.415 AC: 1433 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		2.4
Mutation Taster		=99/1	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: rs12034598; hg19: chr1-207757515;