Variant 12-7089671-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001733.7(C1R):c.487C>T(p.His163Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000191 in 780,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

C1R
NM_001733.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.75

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011308432).

BP6

Variant 12-7089671-G-A is Benign according to our data. Variant chr12-7089671-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039910.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7 linkuse as main transcript	c.487C>T	p.His163Tyr	missense_variant	4/11	ENST00000647956.2	NP_001724.4
C1R	NM_001354346.2 linkuse as main transcript	c.529C>T	p.His177Tyr	missense_variant	4/11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.487C>T	p.His163Tyr	missense_variant	4/11		NM_001733.7	ENSP00000497341	P1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00731

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000414

AC:

103

AN:

248958

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00567

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000178

AC:

112

AN:

628578

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

342416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00291

Gnomad4 SAS exome

AF:

0.0000287

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000243

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00713

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000234

ExAC

AF:

0.000479

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

C1R-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;.;D;D;D;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;.;D;D;D;D;D;D

MetaRNN

Benign

0.011

T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.93

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.1

.;.;D;D;D;D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

.;.;D;D;D;D;D;D

Sift4G

Uncertain

0.0020

.;.;D;.;.;.;.;.

Polyphen

1.0, 0.99

.;.;D;D;.;.;.;.

Vest4

0.27, 0.28, 0.34

MVP

0.96

ClinPred

0.21

GERP RS

5.5

gMVP

0.56

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