1-207585199-T-A

Variant names:

• chr1-207585199-T-A
• rs1746659
• NM_000651.6:c.5530+323T>A

Variant summary

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

The NM_000651.6(CR1):​c.5530+323T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,012 control chromosomes in the GnomAD database, including 16,411 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 (16411 hom., cov: 32)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 8 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=-0.94).
• 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.5530+323T>A		intron_variant	Intron 33 of 46	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.5530+323T>A		intron_variant	Intron 33 of 46	5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60171 AN: 151894 Hom.: 16375 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.319

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

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

GnomAD4 genome AF: 0.396 AC: 60260 AN: 152012 Hom.: 16411 Cov.: 32 AF XY: 0.397 AC XY: 29537 AN XY: 74318

African (AFR) AF: 0.773 AC: 32033 AN: 41448

American (AMR) AF: 0.357 AC: 5453 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1105 AN: 3464

East Asian (EAS) AF: 0.288 AC: 1485 AN: 5156

South Asian (SAS) AF: 0.444 AC: 2132 AN: 4804

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10578

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

European-Non Finnish (NFE) AF: 0.213 AC: 14492 AN: 67964

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

Alfa AF: 0.324 Hom.: 1354

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	-0.94
CADD	Benign	1.2
DANN	Benign	0.87
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: rs1746659; hg19: chr1-207758544;