Variant 12-7088615-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001733.7(C1R):c.1033A>C(p.Ile345Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 723,146 control chromosomes in the GnomAD database, including 415 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 56 hom., cov: 32)

Exomes 𝑓: 0.011 ( 359 hom. )

Consequence

C1R
NM_001733.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.999

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:

C1R (HGNC:):

C1R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a disulfide_bond (size 49) in uniprot entity C1R_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_001733.7

BP4

Computational evidence support a benign effect (MetaRNN=0.0021000206).

BP6

Variant 12-7088615-T-G is Benign according to our data. Variant chr12-7088615-T-G is described in ClinVar as [Benign]. Clinvar id is 1268134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7 linkuse as main transcript	c.1033A>C	p.Ile345Leu	missense_variant	7/11	ENST00000647956.2	NP_001724.4	P00736
C1R	NM_001354346.2 linkuse as main transcript	c.1075A>C	p.Ile359Leu	missense_variant	7/11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.1033A>C	p.Ile345Leu	missense_variant	7/11		NM_001733.7	ENSP00000497341.1		A0A3B3ISR2

Frequencies

GnomAD3 genomes

AF:

0.00925

AC:

1408

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0671

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0251

AC:

4142

AN:

164968

Hom.:

283

AF XY:

0.0202

AC XY:

1750

AN XY:

86742

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0422

Gnomad SAS exome

AF:

0.00667

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000227

Gnomad OTH exome

AF:

0.0204

GnomAD4 exome

AF:

0.0106

AC:

6062

AN:

570866

Hom.:

359

Cov.:

AF XY:

0.00903

AC XY:

2781

AN XY:

308132

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0268

Gnomad4 SAS exome

AF:

0.00745

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.00751

GnomAD4 genome

AF:

0.00927

AC:

1412

AN:

152280

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.0674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.0163

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00153

AC:

ESP6500EA

AF:

0.000605

AC:

ExAC

AF:

0.00925

AC:

1059

Asia WGS

AF:

0.0280

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 33064175) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.9

DANN

Benign

0.67

DEOGEN2

Benign

0.0077

.;.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.82

T;.;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.27

PROVEAN

Benign

0.54

.;.;N;N;.

REVEL

Benign

0.077

Sift

Benign

1.0

.;.;T;T;.

Sift4G

Benign

0.40

.;.;T;.;.

Polyphen

0.0010, 0.013

.;.;B;B;.

Vest4

0.22, 0.23, 0.26

MutPred

0.60

Gain of disorder (P = 0.3422);Gain of disorder (P = 0.3422);.;.;.;

ClinPred

0.0025

GERP RS

-6.8

gMVP

0.11

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