Variant chr12-7090267-G-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.232-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 718,564 control chromosomes in the GnomAD database, including 2,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 1495 hom., cov: 32)

Exomes 𝑓: 0.012 ( 654 hom. )

Consequence

C1R
NM_001733.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.645

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 (BayesDel_noAF=-0.83).

BP6

Variant 12-7090267-G-T is Benign according to our data. Variant chr12-7090267-G-T is described in ClinVar as [Benign]. Clinvar id is 1294595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.232-19C>A		intron_variant		ENST00000647956.2
C1R	NM_001354346.2 linkuse as main transcript	c.274-19C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1R	ENST00000647956.2 linkuse as main transcript	c.232-19C>A		intron_variant			NM_001733.7	P1

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11659

AN:

152002

Hom.:

1487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00657

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0627

GnomAD3 exomes

AF:

0.0191

AC:

3003

AN:

157584

Hom.:

352

AF XY:

0.0144

AC XY:

1202

AN XY:

83232

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.00624

Gnomad EAS exome

AF:

0.00205

Gnomad SAS exome

AF:

0.000706

Gnomad FIN exome

AF:

0.0000616

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.0125

AC:

7079

AN:

566444

Hom.:

654

Cov.:

AF XY:

0.0102

AC XY:

3116

AN XY:

305600

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.00629

Gnomad4 EAS exome

AF:

0.0284

Gnomad4 SAS exome

AF:

0.000874

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000957

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0769

AC:

11693

AN:

152120

Hom.:

1495

Cov.:

AF XY:

0.0746

AC XY:

5551

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00658

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0620

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.0873

Asia WGS

AF:

0.0250

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	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.65

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