1-207565782-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000651.6(CR1):c.3867-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 149,706 control chromosomes in the GnomAD database, including 19,230 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 0.46 (19230 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250880 hom.)
  • Failed GnomAD Quality Control
• Consequence: CR1 NM_000651.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR1	NM_000651.6	c.3867-56A>G		intron_variant		ENST00000367049.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR1	ENST00000367049.9	c.3867-56A>G		intron_variant		5	NM_000651.6	P1
	ENST00000597497.5	n.353-12802T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 69474 AN: 149590 Hom.: 19222 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.517

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.577 AC: 839157 AN: 1454976 Hom.: 250880 AF XY: 0.573 AC XY: 415114 AN XY: 724238

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.464 AC: 69492 AN: 149706 Hom.: 19230 Cov.: 32 AF XY: 0.463 AC XY: 33865 AN XY: 73190

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.510

Alfa AF: 0.504 Hom.: 2691

Bravo AF: 0.452

Asia WGS AF: 0.336 AC: 1168 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.1
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs3886100; hg19: chr1-207739127; COSMIC: COSV65465444; COSMIC: COSV65465444;