rs769707492

Variant names:

• chr12-7088721-G-A
• rs769707492
• NM_001733.7:c.927C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-7088721-G-A
• chr12-7088721-G-C
• chr12-7088721-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001354346.2(C1R):​c.969C>T​(p.Cys323Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 625,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: C1R NM_001354346.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• 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: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.514 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354346.2. 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.927C>T	p.Cys309Cys	synonymous	Exon 7 of 11	NP_001724.4
	C1R	NM_001354346.2		c.969C>T	p.Cys323Cys	synonymous	Exon 7 of 11	NP_001341275.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1R	ENST00000647956.2	MANE Select	c.927C>T	p.Cys309Cys	synonymous	Exon 7 of 11	ENSP00000497341.1
	C1R	ENST00000903851.1		c.1080C>T	p.Cys360Cys	synonymous	Exon 8 of 12	ENSP00000573910.1
	C1R	ENST00000903850.1		c.999C>T	p.Cys333Cys	synonymous	Exon 8 of 12	ENSP00000573909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000567

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000639 AC: 4 AN: 625502 Hom.: 0 Cov.: 0 AF XY: 0.00000587 AC XY: 2 AN XY: 340442

African (AFR) AF: 0.00 AC: 0 AN: 17664

American (AMR) AF: 0.00 AC: 0 AN: 43196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20868

East Asian (EAS) AF: 0.000111 AC: 4 AN: 36010

South Asian (SAS) AF: 0.00 AC: 0 AN: 68898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 348722

Other (OTH) AF: 0.00 AC: 0 AN: 32994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		0.51
PromoterAI		-0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs769707492; hg19: chr12-7241317;