NM_000651.6:c.7353-2973T>C

Variant names:

• chr1-207627544-T-C
• rs17048010
• NM_000651.6:c.7353-2973T>C

Variant summary

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

The NM_000651.6(CR1):​c.7353-2973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 152,344 control chromosomes in the GnomAD database, including 98 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 0.0071 (98 hom., cov: 32)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.162 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.7353-2973T>C		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.7353-2973T>C		intron	N/A	ENSP00000356016.4	E9PDY4
	CR1	ENST00000400960.7	TSL:1	c.6003-2973T>C		intron	N/A	ENSP00000383744.2	P17927
	CR1	ENST00000367051.6	TSL:5	c.6003-2973T>C		intron	N/A	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes AF: 0.00713 AC: 1086 AN: 152226 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.000530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.00713 AC: 1086 AN: 152344 Hom.: 98 Cov.: 32 AF XY: 0.00803 AC XY: 598 AN XY: 74496

African (AFR) AF: 0.000529 AC: 22 AN: 41596

American (AMR) AF: 0.00229 AC: 35 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.171 AC: 888 AN: 5180

South Asian (SAS) AF: 0.00872 AC: 42 AN: 4818

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68032

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00185 Hom.: 1

Bravo AF: 0.00876

Asia WGS AF: 0.0700 AC: 244 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	2.4
DANN	Benign	0.68
PhyloP100		0.94
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: rs17048010; hg19: chr1-207800889;