rs12734030

Variant names:

• chr1-207620619-C-T
• rs12734030
• NM_000651.6:c.7252+554C>T

Variant summary

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

The NM_000651.6(CR1):​c.7252+554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,098 control chromosomes in the GnomAD database, including 2,703 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 0.18 (2703 hom., cov: 32)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6	c.7252+554C>T		intron_variant	Intron 43 of 46	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.7252+554C>T		intron_variant	Intron 43 of 46	5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26682 AN: 151980 Hom.: 2700 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.175 AC: 26692 AN: 152098 Hom.: 2703 Cov.: 32 AF XY: 0.182 AC XY: 13511 AN XY: 74340

African (AFR) AF: 0.114 AC: 4744 AN: 41476

American (AMR) AF: 0.249 AC: 3810 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1446 AN: 5170

South Asian (SAS) AF: 0.433 AC: 2084 AN: 4808

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11213 AN: 68002

Other (OTH) AF: 0.194 AC: 410 AN: 2108

Alfa AF: 0.177 Hom.: 3242

Bravo AF: 0.175

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.36
PhyloP100		-3.1
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: rs12734030; hg19: chr1-207793964;