C1R p.Cys358*

Variant names:

• chr12-7086422-G-T
• NM_001733.7:c.1074C>A
• C1R p.Cys358*

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001733.7(C1R):​c.1074C>A​(p.Cys358*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1R NM_001733.7 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, periodontal type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• autosomal systemic lupus erythematosus type 16

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ehlers-Danlos syndrome, periodontitis type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001733.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1R	NM_001733.7	MANE Select	c.1074C>A	p.Cys358*	stop_gained	Exon 8 of 11	NP_001724.4	A0A3B3ISR2
	C1R	NM_001354346.2		c.1116C>A	p.Cys372*	stop_gained	Exon 8 of 11	NP_001341275.1	B4DPQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1R	ENST00000647956.2	MANE Select	c.1074C>A	p.Cys358*	stop_gained	Exon 8 of 11	ENSP00000497341.1	A0A3B3ISR2
	C1R	ENST00000903851.1		c.1227C>A	p.Cys409*	stop_gained	Exon 9 of 12	ENSP00000573910.1
	C1R	ENST00000903850.1		c.1146C>A	p.Cys382*	stop_gained	Exon 9 of 12	ENSP00000573909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 246404 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124884

African (AFR) AF: 0.00 AC: 0 AN: 7182

American (AMR) AF: 0.00 AC: 0 AN: 7436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9240

East Asian (EAS) AF: 0.00 AC: 0 AN: 22902

South Asian (SAS) AF: 0.00 AC: 0 AN: 3032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158110

Other (OTH) AF: 0.00 AC: 0 AN: 16374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Pathogenic	36
PhyloP100		3.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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