NM_000651.6:c.5604C>T

Variant names:

• chr1-207587459-C-T
• rs12144461
• NM_000651.6:c.5604C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000651.6(CR1):​c.5604C>T​(p.Val1868Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 1,613,872 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (8 hom., cov: 33)
  • Exomes 𝑓: 0.010 (102 hom.)
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302
• Publications: 9 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]

CR1-AS1 (HGNC:40160):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-207587459-C-T is Benign according to our data. Variant chr1-207587459-C-T is described in ClinVar as Benign. ClinVar VariationId is 2639874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.302 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 BG gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.5604C>T	p.Val1868Val	synonymous	Exon 34 of 47	NP_000642.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.5604C>T	p.Val1868Val	synonymous	Exon 34 of 47	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.4254C>T	p.Val1418Val	synonymous	Exon 26 of 39	ENSP00000383744.2
	CR1	ENST00000367051.6	TSL:5	c.4254C>T	p.Val1418Val	synonymous	Exon 26 of 39	ENSP00000356018.1

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1252 AN: 152192 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00798 AC: 1987 AN: 249142 AF XY: 0.00798

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0212

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.00811

GnomAD4 exome AF: 0.0101 AC: 14812 AN: 1461562 Hom.: 102 Cov.: 31 AF XY: 0.00996 AC XY: 7244 AN XY: 727074

African (AFR) AF: 0.00143 AC: 48 AN: 33478

American (AMR) AF: 0.00293 AC: 131 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 420 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.00195 AC: 168 AN: 86240

European-Finnish (FIN) AF: 0.0193 AC: 1030 AN: 53402

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.0112 AC: 12434 AN: 1111752

Other (OTH) AF: 0.00929 AC: 561 AN: 60370

GnomAD4 genome AF: 0.00822 AC: 1252 AN: 152310 Hom.: 8 Cov.: 33 AF XY: 0.00890 AC XY: 663 AN XY: 74476

African (AFR) AF: 0.00200 AC: 83 AN: 41576

American (AMR) AF: 0.00431 AC: 66 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 721 AN: 68028

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0103 Hom.: 3

Bravo AF: 0.00660

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CR1: BP4, BP7, BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.72
DANN	Benign	0.53
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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: rs12144461; hg19: chr1-207760804;