Variant 1-207563931-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000651.6(CR1):c.3654C>T(p.Pro1218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,479,902 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 44 hom., cov: 16)

Exomes 𝑓: 0.0097 ( 1140 hom. )

Consequence

CR1
NM_000651.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-207563931-C-T is Benign according to our data. Variant chr1-207563931-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639871.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0141 (1593/113012) while in subpopulation NFE AF= 0.0186 (1179/63234). AF 95% confidence interval is 0.0178. There are 44 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1	NM_000651.6 linkuse as main transcript	c.3654C>T	p.Pro1218=	synonymous_variant	22/47	ENST00000367049.9	NP_000642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 linkuse as main transcript	c.3654C>T	p.Pro1218=	synonymous_variant	22/47	5	NM_000651.6	ENSP00000356016	P1
	ENST00000597497.5 linkuse as main transcript	n.353-10951G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

1593

AN:

112978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00423

Gnomad AMI

AF:

0.0293

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00958

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00350

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.00727

GnomAD3 exomes

AF:

0.00222

AC:

500

AN:

225682

Hom.:

AF XY:

0.00228

AC XY:

279

AN XY:

122604

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.000871

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.000630

Gnomad NFE exome

AF:

0.00263

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00972

AC:

13280

AN:

1366890

Hom.:

1140

Cov.:

AF XY:

0.00989

AC XY:

6738

AN XY:

681050

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.00615

Gnomad4 ASJ exome

AF:

0.00633

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.00987

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.0141

AC:

1593

AN:

113012

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

696

AN XY:

54762

show subpopulations

Gnomad4 AFR

AF:

0.00421

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00958

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.00725

Alfa

AF:

0.0177

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

CR1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.5

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over