rs7542544

Variant names:

• chr1-207612878-C-A
• rs7542544
• NM_000651.6:c.6575+837C>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.6575+837C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,096 control chromosomes in the GnomAD database, including 18,286 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 0.45 (18286 hom., cov: 33)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.6575+837C>A		intron	N/A	NP_000642.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.6575+837C>A		intron	N/A	ENSP00000356016.4	E9PDY4
	CR1	ENST00000400960.7	TSL:1	c.5225+837C>A		intron	N/A	ENSP00000383744.2	P17927
	CR1	ENST00000367051.6	TSL:5	c.5225+837C>A		intron	N/A	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69123 AN: 151978 Hom.: 18276 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.455 AC: 69144 AN: 152096 Hom.: 18286 Cov.: 33 AF XY: 0.455 AC XY: 33786 AN XY: 74326

African (AFR) AF: 0.177 AC: 7362 AN: 41526

American (AMR) AF: 0.514 AC: 7856 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1708 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5166

South Asian (SAS) AF: 0.453 AC: 2186 AN: 4824

European-Finnish (FIN) AF: 0.577 AC: 6091 AN: 10560

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40350 AN: 67934

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.442 Hom.: 5900

Bravo AF: 0.442

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.30
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: rs7542544; hg19: chr1-207786223;