12-7090444-C-T

Position:

• chr12-7090444-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001733.7(C1R):​c.232-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 592,860 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (411 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (122 hom.)
• Consequence: C1R NM_001733.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.511

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-7090444-C-T is Benign according to our data. Variant chr12-7090444-C-T is described in ClinVar as [Benign]. Clinvar id is 1183244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1R	NM_001733.7	c.232-196G>A		intron_variant		ENST00000647956.2
C1R	NM_001354346.2	c.274-196G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1R	ENST00000647956.2	c.232-196G>A		intron_variant			NM_001733.7	P1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6131 AN: 152142 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.00549 AC: 2421 AN: 440600 Hom.: 122 AF XY: 0.00455 AC XY: 1056 AN XY: 232076

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.00962

Gnomad4 ASJ exome AF: 0.00399

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000462

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000437

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0404 AC: 6146 AN: 152260 Hom.: 411 Cov.: 32 AF XY: 0.0388 AC XY: 2892 AN XY: 74448

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00808 Hom.: 23

Bravo AF: 0.0461

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6487521; hg19: chr12-7243040;