Variant 12-7089608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001733.7(C1R):c.550G>A(p.Glu184Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 780,854 control chromosomes in the GnomAD database, including 6,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1222 hom., cov: 32)

Exomes 𝑓: 0.11 ( 5336 hom. )

Consequence

C1R
NM_001733.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.459

Variant links:

Genes affected

C1R (HGNC:1246): (complement C1r) This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]

C1R links:

C1RL (HGNC:21265): (complement C1r subcomponent like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C1RL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020693302).

BP6

Variant 12-7089608-C-T is Benign according to our data. Variant chr12-7089608-C-T is described in ClinVar as [Benign]. Clinvar id is 1243558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1R	NM_001733.7 linkuse as main transcript	c.550G>A	p.Glu184Lys	missense_variant	4/11	ENST00000647956.2
C1R	NM_001354346.2 linkuse as main transcript	c.592G>A	p.Glu198Lys	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.550G>A	p.Glu184Lys	missense_variant	4/11		NM_001733.7	P1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17210

AN:

152162

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.0715

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0886

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.114

AC:

28449

AN:

248486

Hom.:

2468

AF XY:

0.116

AC XY:

15698

AN XY:

134820

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.0539

Gnomad ASJ exome

AF:

0.0827

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0708

Gnomad NFE exome

AF:

0.0878

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.110

AC:

69127

AN:

628574

Hom.:

5336

Cov.:

AF XY:

0.113

AC XY:

38672

AN XY:

342416

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.0826

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.0744

Gnomad4 NFE exome

AF:

0.0870

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.113

AC:

17227

AN:

152280

Hom.:

1222

Cov.:

AF XY:

0.115

AC XY:

8569

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0712

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.0715

Gnomad4 NFE

AF:

0.0886

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0983

Hom.:

1532

Bravo

AF:

0.114

TwinsUK

AF:

0.0917

AC:

340

ALSPAC

AF:

0.0791

AC:

305

ESP6500AA

AF:

0.140

AC:

575

ESP6500EA

AF:

0.0833

AC:

698

ExAC

AF:

0.117

AC:

14164

Asia WGS

AF:

0.207

AC:

717

AN:

3478

EpiCase

AF:

0.0869

EpiControl

AF:

0.0941

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.24

CADD

Benign

0.19

DANN

Benign

0.60

DEOGEN2

Benign

0.20

.;.;T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.15

T;.;T;T;T

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

0.34

.;.;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.99

.;.;T;T;T

Sift4G

Benign

0.56

.;.;T;.;.

Polyphen

0.0

.;.;B;B;.

Vest4

0.036, 0.033, 0.16

ClinPred

0.00059

GERP RS

-5.2

gMVP

0.37

Splicing

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