Variant chr12-7088459-A-G 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.1038+151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 710,248 control chromosomes in the GnomAD database, including 10,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2258 hom., cov: 32)

Exomes 𝑓: 0.13 ( 7932 hom. )

Consequence

C1R
NM_001733.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.141

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-7088459-A-G is Benign according to our data. Variant chr12-7088459-A-G is described in ClinVar as [Benign]. Clinvar id is 1288064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 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.1038+151T>C		intron_variant		ENST00000647956.2	NP_001724.4	P00736
C1R	NM_001354346.2 linkuse as main transcript	c.1080+151T>C		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+151T>C		intron_variant			NM_001733.7	ENSP00000497341.1		A0A3B3ISR2

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21940

AN:

152048

Hom.:

2248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0901

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0856

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.141

AC:

20179

AN:

143292

Hom.:

2458

AF XY:

0.144

AC XY:

11083

AN XY:

76796

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.0641

Gnomad EAS exome

AF:

0.514

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.0894

Gnomad NFE exome

AF:

0.0890

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.127

AC:

71155

AN:

558082

Hom.:

7932

Cov.:

AF XY:

0.131

AC XY:

39454

AN XY:

301658

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0740

Gnomad4 ASJ exome

AF:

0.0648

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.0901

Gnomad4 NFE exome

AF:

0.0848

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.144

AC:

21979

AN:

152166

Hom.:

2258

Cov.:

AF XY:

0.148

AC XY:

11006

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.0915

Gnomad4 ASJ

AF:

0.0666

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.0901

Gnomad4 NFE

AF:

0.0856

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.102

Hom.:

1067

Bravo

AF:

0.147

Asia WGS

AF:

0.317

AC:

1104

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

-0.86

CADD

Benign

0.52

DANN

Benign

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