Variant 12-7088532-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+78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 718,430 control chromosomes in the GnomAD database, including 395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 55 hom., cov: 32)

Exomes 𝑓: 0.010 ( 340 hom. )

Consequence

C1R
NM_001733.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0830

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=-0.83).

BP6

Variant 12-7088532-A-G is Benign according to our data. Variant chr12-7088532-A-G is described in ClinVar as [Benign]. Clinvar id is 1183801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0619 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+78T>C		intron_variant		ENST00000647956.2	NP_001724.4	P00736
C1R	NM_001354346.2 linkuse as main transcript	c.1080+78T>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+78T>C		intron_variant			NM_001733.7	ENSP00000497341.1		A0A3B3ISR2

Frequencies

GnomAD3 genomes

AF:

0.00917

AC:

1396

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0401

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0254

AC:

3971

AN:

156086

Hom.:

266

AF XY:

0.0204

AC XY:

1681

AN XY:

82514

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0456

Gnomad SAS exome

AF:

0.00707

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0104

AC:

5902

AN:

566156

Hom.:

340

Cov.:

AF XY:

0.00884

AC XY:

2700

AN XY:

305424

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0283

Gnomad4 SAS exome

AF:

0.00771

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00743

GnomAD4 genome

AF:

0.00920

AC:

1401

AN:

152274

Hom.:

Cov.:

AF XY:

0.00994

AC XY:

740

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.0652

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0400

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00530

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.0290

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

DANN

Benign

0.43

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