Variant chr12-7088490-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001733.7(C1R):c.1038+120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 715,662 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 6 hom. )

Consequence

C1R
NM_001733.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.135

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-7088490-T-C is Benign according to our data. Variant chr12-7088490-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1694657.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 683 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7 linkuse as main transcript	c.1038+120A>G		intron_variant		ENST00000647956.2	NP_001724.4	P00736
C1R	NM_001354346.2 linkuse as main transcript	c.1080+120A>G		intron_variant			NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.1038+120A>G		intron_variant			NM_001733.7	ENSP00000497341.1		A0A3B3ISR2

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

683

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00437

AC:

662

AN:

151390

Hom.:

AF XY:

0.00429

AC XY:

345

AN XY:

80418

show subpopulations

Gnomad AFR exome

AF:

0.000783

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00224

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000571

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.00590

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00500

AC:

2816

AN:

563378

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

1422

AN XY:

304104

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000542

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.00594

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.00449

AC:

683

AN:

152284

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00531

Hom.:

Bravo

AF:

0.00345

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 01, 2024

C1R: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.4

DANN

Benign

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