1-207629207-A-C

Variant names:

• chr1-207629207-A-C
• rs4844610
• NM_000651.6:c.7353-1310A>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.7353-1310A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,118 control chromosomes in the GnomAD database, including 58,187 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 0.87 (58187 hom., cov: 30)
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 49 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 (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6	c.7353-1310A>C		intron_variant	Intron 45 of 46	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9	c.7353-1310A>C		intron_variant	Intron 45 of 46	5	NM_000651.6	ENSP00000356016.4

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132432 AN: 152000 Hom.: 58129 Cov.: 30

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.871 AC: 132549 AN: 152118 Hom.: 58187 Cov.: 30 AF XY: 0.873 AC XY: 64942 AN XY: 74358

African (AFR) AF: 0.968 AC: 40184 AN: 41514

American (AMR) AF: 0.880 AC: 13448 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2871 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4992 AN: 5174

South Asian (SAS) AF: 0.931 AC: 4470 AN: 4802

European-Finnish (FIN) AF: 0.809 AC: 8555 AN: 10570

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55197 AN: 67980

Other (OTH) AF: 0.876 AC: 1853 AN: 2116

Alfa AF: 0.838 Hom.: 19806

Bravo AF: 0.882

Asia WGS AF: 0.936 AC: 3254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		-0.13
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: rs4844610; hg19: chr1-207802552;