1-207526856-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000651.6(CR1):c.990C>T(p.Tyr330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (1 hom., cov: 18)
  • Exomes 𝑓: 0.00043 (40 hom.)
  • Failed GnomAD Quality Control
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-207526856-C-T is Benign according to our data. Variant chr1-207526856-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.85 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CR1	NM_000651.6	c.990C>T	p.Tyr330=	synonymous_variant	6/47	ENST00000367049.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CR1	ENST00000367049.9	c.990C>T	p.Tyr330=	synonymous_variant	6/47	5	NM_000651.6	P1

Frequencies

GnomAD3 genomes AF: 0.000357 AC: 43 AN: 120596 Hom.: 1 Cov.: 18

Gnomad AFR AF: 0.0000881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000403

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000298

Gnomad FIN AF: 0.000219

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000478

Gnomad OTH AF: 0.00175

GnomAD3 exomes AF: 0.000144 AC: 32 AN: 221896 Hom.: 1 AF XY: 0.000116 AC XY: 14 AN XY: 120696

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000199

Gnomad FIN exome AF: 0.0000992

Gnomad NFE exome AF: 0.000104

Gnomad OTH exome AF: 0.000718

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000427 AC: 584 AN: 1369178 Hom.: 40 Cov.: 31 AF XY: 0.000426 AC XY: 290 AN XY: 680720

Gnomad4 AFR exome AF: 0.000488

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.0000839

Gnomad4 EAS exome AF: 0.000106

Gnomad4 SAS exome AF: 0.000799

Gnomad4 FIN exome AF: 0.000220

Gnomad4 NFE exome AF: 0.000356

Gnomad4 OTH exome AF: 0.000625

GnomAD4 genome AF: 0.000356 AC: 43 AN: 120664 Hom.: 1 Cov.: 18 AF XY: 0.000308 AC XY: 18 AN XY: 58366

Gnomad4 AFR AF: 0.0000878

Gnomad4 AMR AF: 0.000403

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000298

Gnomad4 FIN AF: 0.000219

Gnomad4 NFE AF: 0.000478

Gnomad4 OTH AF: 0.00174

Alfa AF: 0.000876 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

CR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.87
Dann	Benign	0.41

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: rs755952223; hg19: chr1-207700201;