Variant 12-7081258-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001733.7(C1R):c.1392C>A(p.Ile464Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,612,366 control chromosomes in the GnomAD database, including 1,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 138 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1110 hom. )

Consequence

C1R
NM_001733.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.07

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-7081258-G-T is Benign according to our data. Variant chr12-7081258-G-T is described in ClinVar as [Benign]. Clinvar id is 1235256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0771 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.1392C>A	p.Ile464Ile	synonymous_variant	11/11	ENST00000647956.2	NP_001724.4	P00736
C1R	NM_001354346.2 linkuse as main transcript	c.1434C>A	p.Ile478Ile	synonymous_variant	11/11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.1392C>A	p.Ile464Ile	synonymous_variant	11/11		NM_001733.7	ENSP00000497341.1		A0A3B3ISR2

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6204

AN:

152150

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0585

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.0563

Gnomad SAS

AF:

0.0837

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0390

AC:

9513

AN:

243918

Hom.:

238

AF XY:

0.0409

AC XY:

5426

AN XY:

132646

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0746

Gnomad EAS exome

AF:

0.0503

Gnomad SAS exome

AF:

0.0785

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0299

Gnomad OTH exome

AF:

0.0488

GnomAD4 exome

AF:

0.0330

AC:

48119

AN:

1460098

Hom.:

1110

Cov.:

AF XY:

0.0343

AC XY:

24899

AN XY:

726176

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.0731

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.0754

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0467

GnomAD4 genome

AF:

0.0408

AC:

6209

AN:

152268

Hom.:

138

Cov.:

AF XY:

0.0412

AC XY:

3068

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0585

Gnomad4 AMR

AF:

0.0368

Gnomad4 ASJ

AF:

0.0663

Gnomad4 EAS

AF:

0.0565

Gnomad4 SAS

AF:

0.0838

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.0296

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0343

Hom.:

201

Bravo

AF:

0.0419

Asia WGS

AF:

0.0790

AC:

273

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.3

DANN

Benign

0.73

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